TDMS Study 99035-01 Pathology Tables
NTP STATISTICAL ANALYSIS OF NON-NEOPLASTIC LESIONS REPORT: PEIRPT10 LAB: Battelle Columbus TRANSGENIC MODEL EVALUATION II (GLYCIDOL) DATE: 04/14/04 EXPERIMENT: 99035 TEST: 01 TIME: 10:53:58 TEST TYPE: 26-39 WEEKS CAGES FROM 0000 TO LAST CAGE PAGE: 1 CONT: N01-ES-65406 ROUTE: GAVAGE NTP C#: C99035 PATHOLOGIST: MISSING CAS: 556-52-5 ------------------------------------------------------------------------------------------------------------------------------------ FINAL #1 MICE REASONS FOR REMOVAL: ALL REMOVAL DATE RANGE: ALL TREATMENT GROUPS: INCLUDE ALL NTP STATISTICAL ANALYSIS OF NON-NEOPLASTIC LESIONS REPORT: PEIRPT10 LAB: Battelle Columbus TRANSGENIC MODEL EVALUATION II (GLYCIDOL) DATE: 04/14/04 EXPERIMENT: 99035 TEST: 01 TIME: 10:53:58 TEST TYPE: 26-39 WEEKS CAGES FROM 0000 TO LAST CAGE CONT: N01-ES-65406 ROUTE: GAVAGE NTP C#: C99035 PATHOLOGIST: MISSING CAS: 556-52-5 SUMMARY OF STATISTICALLY SIGNIFICANT (P<=.05) RESULTS IN THE ANALYSIS OF TRANSGENIC MODEL EVALUATION II (GLY =============================================================== Male Mice ------------ Organ Morphology ----- ---------- Brain: Cerebellum Gliosis Neuronopathy Brain: Cerebrum Necrosis Focal Brain: Medulla Gliosis Neuronopathy Brain: Thalamus Gliosis Neuronopathy Heart: Myocardium Degeneration Mineralization Necrosis Liver Inflammation Chronic Necrosis Focal Spleen Atrophy Stomach, Forestomach Ulcer Stomach, Forestomach: Epithelium Hyperplasia Stomach, Glandular Mineralization Thymus Atrophy =============================================================== Female Mice ------------ Organ Morphology ----- ---------- Adrenal Cortex: Subcapsular Hyperplasia Brain: Cerebellum Neuronopathy Brain: Medulla Gliosis Neuronopathy Brain: Thalamus Neuronopathy Kidney: Renal Tubule Accumulation, Hyaline Droplet Liver Angiectasis Focal Necrosis Focal Lung Inflammation Lymph Node: Mediastinal Hyperplasia Lymphoid Ovary Cyst Spleen Hematopoietic Cell Proliferation Stomach, Forestomach: Epithelium Hyperplasia Stomach, Glandular Mineralization Stomach, Glandular: Muscularis Mineralization Thymus Atrophy =============================================================== Date: 04/14/04 EXPERIMENT: 99035 TEST: 01 Page 1 Statistical Analysis of Non-neoplastic Lesions in Mice(P16(INK4A)/(+/-) (C57BL/6)) - TRANSGENIC MODEL EVALUATION II (GLY Terminal Sacrifice at 40 weeks |=================================================================================================================================| | | | | | Males | |Dose | 0 MG/KG 25 MG/KG 50 MG/KG 100 200 | | | MG/KG MG/KG | |=================================================================================================================================| | | |Adrenal Cortex | | Hyperplasia Focal | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 1/15 (7%) 0/15 (0%) 0/15 (0%) 1/14 (7%) 0/15 (0%) | |POLY-3 RATE (b) | 1/13.95 0/14.74 0/13.80 1/14.00 0/11.42 | |POLY-3 PERCENT (g) | 7.2% 0.0% 0.0% 7.1% 0.0% | |TERMINAL (d) | 1/13 (8%) 0/14 (0%) 0/13 (0%) 1/14 (7%) 0/7 (0%) | |FIRST INCIDENCE | 280 (T) --- --- 280 (T) --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.617N P=0.485N P=0.500N P=0.748N P=0.623N | |POLY 3 | P=0.533N P=0.489N P=0.502N P=0.760N P=0.540N | |POLY 1.5 | P=0.522N P=0.493N P=0.502N P=0.755 P=0.522N | |POLY 6 | P=0.545N P=0.485N P=0.500N P=0.752N P=0.562N | |LOGISTIC REGRESSION| P=0.617N (e) (e) P=0.748N (e) | |COCH-ARM / FISHERS | P=0.503N P=0.500N P=0.500N P=0.741 P=0.500N | |ORDER RESTRICTED | P=0.271N (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 MG/KG 25 MG/KG 50 MG/KG 100 200 | | | MG/KG MG/KG | |=================================================================================================================================| | | |Adrenal Cortex | | Hyperplasia Focal | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/15 (0%) 2/15 (13%) 0/15 (0%) 0/15 (0%) 1/15 (7%) | |POLY-3 RATE (b) | 0/13.88 2/14.62 0/14.15 0/14.62 1/12.41 | |POLY-3 PERCENT (g) | 0.0% 13.7% 0.0% 0.0% 8.1% | |TERMINAL (d) | 0/13 (0%) 2/14 (14%) 0/12 (0%) 0/14 (0%) 1/9 (11%) | |FIRST INCIDENCE | --- 281 (T) --- --- 281 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.503 P=0.252 (e) (e) P=0.427 | |POLY 3 | P=0.566 P=0.243 (e) (e) P=0.478 | |POLY 1.5 | P=0.576 P=0.243 (e) (e) P=0.488 | |POLY 6 | P=0.556 P=0.242 (e) (e) P=0.466 | |LOGISTIC REGRESSION| (e) P=0.252 (e) (e) P=0.427 | |COCH-ARM / FISHERS | P=0.583 P=0.241 (e) (e) P=0.500 | |ORDER RESTRICTED | P=0.277 (e) (e) (e) (e) | |=================================================================================================================================| Date: 04/14/04 EXPERIMENT: 99035 TEST: 01 Page 2 Statistical Analysis of Non-neoplastic Lesions in Mice(P16(INK4A)/(+/-) (C57BL/6)) - TRANSGENIC MODEL EVALUATION II ( GLY Terminal Sacrifice at 40 weeks |=================================================================================================================================| | | | | | Males | |Dose | 0 MG/KG 25 MG/KG 50 MG/KG 100 200 | | | MG/KG MG/KG | |=================================================================================================================================| | | |Adrenal Cortex: Subcapsular | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 1/15 (7%) 2/15 (13%) 2/15 (13%) 3/14 (21%) 1/15 (7%) | |POLY-3 RATE (b) | 1/13.95 2/14.74 2/13.80 3/14.00 1/11.42 | |POLY-3 PERCENT (g) | 7.2% 13.6% 14.5% 21.4% 8.8% | |TERMINAL (d) | 1/13 (8%) 2/14 (14%) 2/13 (15%) 3/14 (21%) 1/7 (14%) | |FIRST INCIDENCE | 280 (T) 280 (T) 280 (T) 280 (T) 280 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.408 P=0.527 P=0.500 P=0.325 P=0.620 | |POLY 3 | P=0.499 P=0.519 P=0.496 P=0.298 P=0.715 | |POLY 1.5 | P=0.560 P=0.512 P=0.496 P=0.288 P=0.736 | |POLY 6 | P=0.423 P=0.527 P=0.499 P=0.311 P=0.686 | |LOGISTIC REGRESSION| P=0.408 P=0.527 P=0.500 P=0.325 P=0.620 | |COCH-ARM / FISHERS | P=0.556N P=0.500 P=0.500 P=0.272 P=0.759N | |ORDER RESTRICTED | P=0.480 (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 MG/KG 25 MG/KG 50 MG/KG 100 200 | | | MG/KG MG/KG | |=================================================================================================================================| | | |Adrenal Cortex: Subcapsular | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 15/15 (100%) 15/15 (100%) 10/15 (67%) 14/15 (93%) 15/15 (100%) | |POLY-3 RATE (b) | 15/15.00 15/15.00 10/14.59 14/15.00 15/15.00 | |POLY-3 PERCENT (g) | 100.0% 100.0% 68.6% 93.3% 100.0% | |TERMINAL (d) | 13/13 (100%) 14/14 (100%) 9/12 (75%) 13/14 (93%) 9/9 (100%) | |FIRST INCIDENCE | 83 239 232 239 133 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.017 * (e) P=0.097N P=0.309N (e) | |POLY 3 | P=0.396 (e) P=0.020N* P=0.500N (e) | |POLY 1.5 | P=0.384 (e) P=0.018N* P=0.500N (e) | |POLY 6 | P=0.414 (e) P=0.025N* P=0.500N (e) | |LOGISTIC REGRESSION| P=0.392 (e) P=0.025N* (e) (e) | |COCH-ARM / FISHERS | P=0.382 (e) P=0.021N* P=0.500N (e) | |ORDER RESTRICTED | P=0.115N (e) (e) (e) (e) | |=================================================================================================================================| Date: 04/14/04 EXPERIMENT: 99035 TEST: 01 Page 3 Statistical Analysis of Non-neoplastic Lesions in Mice(P16(INK4A)/(+/-) (C57BL/6)) - TRANSGENIC MODEL EVALUATION II ( GLY Terminal Sacrifice at 40 weeks |=================================================================================================================================| | | | | | Males | |Dose | 0 MG/KG 25 MG/KG 50 MG/KG 100 200 | | | MG/KG MG/KG | |=================================================================================================================================| | | |Brain: Cerebellum | | Gliosis | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/15 (0%) 0/15 (0%) 0/15 (0%) 0/15 (0%) 2/15 (13%) | |POLY-3 RATE (b) | 0/13.95 0/14.74 0/13.80 0/14.37 2/12.20 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 0.0% 16.4% | |TERMINAL (d) | 0/13 (0%) 0/14 (0%) 0/13 (0%) 0/14 (0%) 0/7 (0%) | |FIRST INCIDENCE | --- --- --- --- 210 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.013 * (e) (e) (e) P=0.192 | |POLY 3 | P=0.016 * (e) (e) (e) P=0.200 | |POLY 1.5 | P=0.017 * (e) (e) (e) P=0.213 | |POLY 6 | P=0.016 * (e) (e) (e) P=0.185 | |LOGISTIC REGRESSION| P=0.053 (e) (e) (e) P=0.345 | |COCH-ARM / FISHERS | P=0.021 * (e) (e) (e) P=0.241 | |ORDER RESTRICTED | P=0.009 ** (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 MG/KG 25 MG/KG 50 MG/KG 100 200 | | | MG/KG MG/KG | |=================================================================================================================================| | | |Brain: Cerebellum | | Gliosis | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/15 (0%) 0/15 (0%) 0/15 (0%) 0/15 (0%) 1/15 (7%) | |POLY-3 RATE (b) | 0/13.88 0/14.62 0/14.15 0/14.62 1/13.01 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 0.0% 7.7% | |TERMINAL (d) | 0/13 (0%) 0/14 (0%) 0/12 (0%) 0/14 (0%) 0/9 (0%) | |FIRST INCIDENCE | --- --- --- --- 208 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.129 (e) (e) (e) P=0.485 | |POLY 3 | P=0.135 (e) (e) (e) P=0.487 | |POLY 1.5 | P=0.138 (e) (e) (e) P=0.494 | |POLY 6 | P=0.132 (e) (e) (e) P=0.480 | |LOGISTIC REGRESSION| P=0.177 (e) (e) (e) P=0.498 | |COCH-ARM / FISHERS | P=0.143 (e) (e) (e) P=0.500 | |ORDER RESTRICTED | P=0.077 (e) (e) (e) (e) | |=================================================================================================================================| Date: 04/14/04 EXPERIMENT: 99035 TEST: 01 Page 4 Statistical Analysis of Non-neoplastic Lesions in Mice(P16(INK4A)/(+/-) (C57BL/6)) - TRANSGENIC MODEL EVALUATION II ( GLY Terminal Sacrifice at 40 weeks |=================================================================================================================================| | | | | | Males | |Dose | 0 MG/KG 25 MG/KG 50 MG/KG 100 200 | | | MG/KG MG/KG | |=================================================================================================================================| | | |Brain: Cerebellum | | Neuronopathy | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/15 (0%) 0/15 (0%) 0/15 (0%) 0/15 (0%) 3/15 (20%) | |POLY-3 RATE (b) | 0/13.95 0/14.74 0/13.80 0/14.37 3/12.93 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 0.0% 23.2% | |TERMINAL (d) | 0/13 (0%) 0/14 (0%) 0/13 (0%) 0/14 (0%) 0/7 (0%) | |FIRST INCIDENCE | --- --- --- --- 181 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.002 ** (e) (e) (e) P=0.099 | |POLY 3 | P=0.002 ** (e) (e) (e) P=0.090 | |POLY 1.5 | P=0.002 ** (e) (e) (e) P=0.097 | |POLY 6 | P=0.002 ** (e) (e) (e) P=0.082 | |LOGISTIC REGRESSION| P=0.019 * (e) (e) (e) P=0.277 | |COCH-ARM / FISHERS | P=0.003 ** (e) (e) (e) P=0.112 | |ORDER RESTRICTED | P=0.002 ** (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 MG/KG 25 MG/KG 50 MG/KG 100 200 | | | MG/KG MG/KG | |=================================================================================================================================| | | |Brain: Cerebellum | | Neuronopathy | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/15 (0%) 0/15 (0%) 0/15 (0%) 1/15 (7%) 3/15 (20%) | |POLY-3 RATE (b) | 0/13.88 0/14.62 0/14.15 1/14.62 3/13.90 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 6.8% 21.6% | |TERMINAL (d) | 0/13 (0%) 0/14 (0%) 0/12 (0%) 1/14 (7%) 1/9 (11%) | |FIRST INCIDENCE | --- --- --- 281 (T) 133 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.003 ** (e) (e) P=0.515 P=0.102 | |POLY 3 | P=0.004 ** (e) (e) P=0.510 P=0.105 | |POLY 1.5 | P=0.004 ** (e) (e) P=0.510 P=0.108 | |POLY 6 | P=0.004 ** (e) (e) P=0.509 P=0.100 | |LOGISTIC REGRESSION| P=0.012 * (e) (e) P=0.515 P=0.104 | |COCH-ARM / FISHERS | P=0.005 ** (e) (e) P=0.500 P=0.112 | |ORDER RESTRICTED | P=0.008 ** (e) (e) (e) (e) | |=================================================================================================================================| Date: 04/14/04 EXPERIMENT: 99035 TEST: 01 Page 5 Statistical Analysis of Non-neoplastic Lesions in Mice(P16(INK4A)/(+/-) (C57BL/6)) - TRANSGENIC MODEL EVALUATION II ( GLY Terminal Sacrifice at 40 weeks |=================================================================================================================================| | | | | | Males | |Dose | 0 MG/KG 25 MG/KG 50 MG/KG 100 200 | | | MG/KG MG/KG | |=================================================================================================================================| | | |Brain: Cerebrum | | Necrosis Focal | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/15 (0%) 0/15 (0%) 0/15 (0%) 0/15 (0%) 2/15 (13%) | |POLY-3 RATE (b) | 0/13.95 0/14.74 0/13.80 0/14.37 2/12.04 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 0.0% 16.6% | |TERMINAL (d) | 0/13 (0%) 0/14 (0%) 0/13 (0%) 0/14 (0%) 0/7 (0%) | |FIRST INCIDENCE | --- --- --- --- 210 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.011 * (e) (e) (e) P=0.180 | |POLY 3 | P=0.016 * (e) (e) (e) P=0.197 | |POLY 1.5 | P=0.017 * (e) (e) (e) P=0.211 | |POLY 6 | P=0.016 * (e) (e) (e) P=0.180 | |LOGISTIC REGRESSION| P=0.046 * (e) (e) (e) P=0.306 | |COCH-ARM / FISHERS | P=0.021 * (e) (e) (e) P=0.241 | |ORDER RESTRICTED | P=0.009 ** (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 MG/KG 25 MG/KG 50 MG/KG 100 200 | | | MG/KG MG/KG | |=================================================================================================================================| | | |Brain: Cerebrum | | Necrosis Focal | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/15 (0%) 0/15 (0%) 0/15 (0%) 0/15 (0%) 0/15 (0%) | |POLY-3 RATE (b) | 0/13.88 0/14.62 0/14.15 0/14.62 0/12.41 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 0/13 (0%) 0/14 (0%) 0/12 (0%) 0/14 (0%) 0/9 (0%) | |FIRST INCIDENCE | --- --- --- --- --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | (e) (e) (e) (e) (e) | |POLY 3 | (e) (e) (e) (e) (e) | |POLY 1.5 | (e) (e) (e) (e) (e) | |POLY 6 | (e) (e) (e) (e) (e) | |LOGISTIC REGRESSION| (e) (e) (e) (e) (e) | |COCH-ARM / FISHERS | (e) (e) (e) (e) (e) | |ORDER RESTRICTED | (e) (e) (e) (e) (e) | |=================================================================================================================================| Date: 04/14/04 EXPERIMENT: 99035 TEST: 01 Page 6 Statistical Analysis of Non-neoplastic Lesions in Mice(P16(INK4A)/(+/-) (C57BL/6)) - TRANSGENIC MODEL EVALUATION II ( GLY Terminal Sacrifice at 40 weeks |=================================================================================================================================| | | | | | Males | |Dose | 0 MG/KG 25 MG/KG 50 MG/KG 100 200 | | | MG/KG MG/KG | |=================================================================================================================================| | | |Brain: Medulla | | Gliosis | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/15 (0%) 0/15 (0%) 0/15 (0%) 0/15 (0%) 2/15 (13%) | |POLY-3 RATE (b) | 0/13.95 0/14.74 0/13.80 0/14.37 2/12.73 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 0.0% 15.7% | |TERMINAL (d) | 0/13 (0%) 0/14 (0%) 0/13 (0%) 0/14 (0%) 0/7 (0%) | |FIRST INCIDENCE | --- --- --- --- 181 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.021 * (e) (e) (e) P=0.232 | |POLY 3 | P=0.017 * (e) (e) (e) P=0.209 | |POLY 1.5 | P=0.018 * (e) (e) (e) P=0.219 | |POLY 6 | P=0.016 * (e) (e) (e) P=0.195 | |LOGISTIC REGRESSION| P=0.062 (e) (e) (e) P=0.476 | |COCH-ARM / FISHERS | P=0.021 * (e) (e) (e) P=0.241 | |ORDER RESTRICTED | P=0.010 * (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 MG/KG 25 MG/KG 50 MG/KG 100 200 | | | MG/KG MG/KG | |=================================================================================================================================| | | |Brain: Medulla | | Gliosis | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/15 (0%) 0/15 (0%) 0/15 (0%) 0/15 (0%) 2/15 (13%) | |POLY-3 RATE (b) | 0/13.88 0/14.62 0/14.15 0/14.62 2/13.31 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 0.0% 15.0% | |TERMINAL (d) | 0/13 (0%) 0/14 (0%) 0/12 (0%) 0/14 (0%) 1/9 (11%) | |FIRST INCIDENCE | --- --- --- --- 133 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.015 * (e) (e) (e) P=0.207 | |POLY 3 | P=0.018 * (e) (e) (e) P=0.221 | |POLY 1.5 | P=0.018 * (e) (e) (e) P=0.229 | |POLY 6 | P=0.017 * (e) (e) (e) P=0.210 | |LOGISTIC REGRESSION| P=0.037 * (e) (e) (e) P=0.225 | |COCH-ARM / FISHERS | P=0.021 * (e) (e) (e) P=0.241 | |ORDER RESTRICTED | P=0.012 * (e) (e) (e) (e) | |=================================================================================================================================| Date: 04/14/04 EXPERIMENT: 99035 TEST: 01 Page 7 Statistical Analysis of Non-neoplastic Lesions in Mice(P16(INK4A)/(+/-) (C57BL/6)) - TRANSGENIC MODEL EVALUATION II ( GLY Terminal Sacrifice at 40 weeks |=================================================================================================================================| | | | | | Males | |Dose | 0 MG/KG 25 MG/KG 50 MG/KG 100 200 | | | MG/KG MG/KG | |=================================================================================================================================| | | |Brain: Medulla | | Neuronopathy | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/15 (0%) 0/15 (0%) 0/15 (0%) 0/15 (0%) 3/15 (20%) | |POLY-3 RATE (b) | 0/13.95 0/14.74 0/13.80 0/14.37 3/12.93 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 0.0% 23.2% | |TERMINAL (d) | 0/13 (0%) 0/14 (0%) 0/13 (0%) 0/14 (0%) 0/7 (0%) | |FIRST INCIDENCE | --- --- --- --- 181 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.002 ** (e) (e) (e) P=0.099 | |POLY 3 | P=0.002 ** (e) (e) (e) P=0.090 | |POLY 1.5 | P=0.002 ** (e) (e) (e) P=0.097 | |POLY 6 | P=0.002 ** (e) (e) (e) P=0.082 | |LOGISTIC REGRESSION| P=0.019 * (e) (e) (e) P=0.277 | |COCH-ARM / FISHERS | P=0.003 ** (e) (e) (e) P=0.112 | |ORDER RESTRICTED | P=0.002 ** (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 MG/KG 25 MG/KG 50 MG/KG 100 200 | | | MG/KG MG/KG | |=================================================================================================================================| | | |Brain: Medulla | | Neuronopathy | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/15 (0%) 0/15 (0%) 0/15 (0%) 0/15 (0%) 3/15 (20%) | |POLY-3 RATE (b) | 0/13.88 0/14.62 0/14.15 0/14.62 3/14.02 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 0.0% 21.4% | |TERMINAL (d) | 0/13 (0%) 0/14 (0%) 0/12 (0%) 0/14 (0%) 1/9 (11%) | |FIRST INCIDENCE | --- --- --- --- 133 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.002 ** (e) (e) (e) P=0.106 | |POLY 3 | P=0.002 ** (e) (e) (e) P=0.106 | |POLY 1.5 | P=0.002 ** (e) (e) (e) P=0.110 | |POLY 6 | P=0.002 ** (e) (e) (e) P=0.101 | |LOGISTIC REGRESSION| P=0.007 ** (e) (e) (e) P=0.099 | |COCH-ARM / FISHERS | P=0.003 ** (e) (e) (e) P=0.112 | |ORDER RESTRICTED | P=0.003 ** (e) (e) (e) (e) | |=================================================================================================================================| Date: 04/14/04 EXPERIMENT: 99035 TEST: 01 Page 8 Statistical Analysis of Non-neoplastic Lesions in Mice(P16(INK4A)/(+/-) (C57BL/6)) - TRANSGENIC MODEL EVALUATION II ( GLY Terminal Sacrifice at 40 weeks |=================================================================================================================================| | | | | | Males | |Dose | 0 MG/KG 25 MG/KG 50 MG/KG 100 200 | | | MG/KG MG/KG | |=================================================================================================================================| | | |Brain: Thalamus | | Gliosis | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/15 (0%) 0/15 (0%) 0/15 (0%) 0/15 (0%) 2/15 (13%) | |POLY-3 RATE (b) | 0/13.95 0/14.74 0/13.80 0/14.37 2/12.59 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 0.0% 15.9% | |TERMINAL (d) | 0/13 (0%) 0/14 (0%) 0/13 (0%) 0/14 (0%) 0/7 (0%) | |FIRST INCIDENCE | --- --- --- --- 208 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.020 * (e) (e) (e) P=0.232 | |POLY 3 | P=0.017 * (e) (e) (e) P=0.207 | |POLY 1.5 | P=0.018 * (e) (e) (e) P=0.217 | |POLY 6 | P=0.016 * (e) (e) (e) P=0.194 | |LOGISTIC REGRESSION| P=0.065 (e) (e) (e) P=0.475 | |COCH-ARM / FISHERS | P=0.021 * (e) (e) (e) P=0.241 | |ORDER RESTRICTED | P=0.010 * (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 MG/KG 25 MG/KG 50 MG/KG 100 200 | | | MG/KG MG/KG | |=================================================================================================================================| | | |Brain: Thalamus | | Gliosis | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/15 (0%) 0/15 (0%) 0/15 (0%) 0/15 (0%) 1/15 (7%) | |POLY-3 RATE (b) | 0/13.88 0/14.62 0/14.15 0/14.62 1/13.12 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 0.0% 7.6% | |TERMINAL (d) | 0/13 (0%) 0/14 (0%) 0/12 (0%) 0/14 (0%) 0/9 (0%) | |FIRST INCIDENCE | --- --- --- --- 186 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.138 (e) (e) (e) P=0.500 | |POLY 3 | P=0.136 (e) (e) (e) P=0.489 | |POLY 1.5 | P=0.139 (e) (e) (e) P=0.495 | |POLY 6 | P=0.133 (e) (e) (e) P=0.481 | |LOGISTIC REGRESSION| P=0.170 (e) (e) (e) P=0.481 | |COCH-ARM / FISHERS | P=0.143 (e) (e) (e) P=0.500 | |ORDER RESTRICTED | P=0.079 (e) (e) (e) (e) | |=================================================================================================================================| Date: 04/14/04 EXPERIMENT: 99035 TEST: 01 Page 9 Statistical Analysis of Non-neoplastic Lesions in Mice(P16(INK4A)/(+/-) (C57BL/6)) - TRANSGENIC MODEL EVALUATION II ( GLY Terminal Sacrifice at 40 weeks |=================================================================================================================================| | | | | | Males | |Dose | 0 MG/KG 25 MG/KG 50 MG/KG 100 200 | | | MG/KG MG/KG | |=================================================================================================================================| | | |Brain: Thalamus | | Neuronopathy | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/15 (0%) 0/15 (0%) 0/15 (0%) 0/15 (0%) 5/15 (33%) | |POLY-3 RATE (b) | 0/13.95 0/14.74 0/13.80 0/14.37 5/13.56 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 0.0% 36.9% | |TERMINAL (d) | 0/13 (0%) 0/14 (0%) 0/13 (0%) 0/14 (0%) 0/7 (0%) | |FIRST INCIDENCE | --- --- --- --- 181 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P<0.001 ** (e) (e) (e) P=0.022 * | |POLY 3 | P<0.001 ** (e) (e) (e) P=0.014 * | |POLY 1.5 | P<0.001 ** (e) (e) (e) P=0.015 * | |POLY 6 | P<0.001 ** (e) (e) (e) P=0.012 * | |LOGISTIC REGRESSION| P<0.001 ** (e) (e) (e) P=0.077 | |COCH-ARM / FISHERS | P<0.001 ** (e) (e) (e) P=0.021 * | |ORDER RESTRICTED | P<0.001 ** (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 MG/KG 25 MG/KG 50 MG/KG 100 200 | | | MG/KG MG/KG | |=================================================================================================================================| | | |Brain: Thalamus | | Neuronopathy | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/15 (0%) 0/15 (0%) 0/15 (0%) 0/15 (0%) 3/15 (20%) | |POLY-3 RATE (b) | 0/13.88 0/14.62 0/14.15 0/14.62 3/14.61 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 0.0% 20.5% | |TERMINAL (d) | 0/13 (0%) 0/14 (0%) 0/12 (0%) 0/14 (0%) 0/9 (0%) | |FIRST INCIDENCE | --- --- --- --- 133 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.003 ** (e) (e) (e) P=0.124 | |POLY 3 | P=0.002 ** (e) (e) (e) P=0.115 | |POLY 1.5 | P=0.002 ** (e) (e) (e) P=0.115 | |POLY 6 | P=0.002 ** (e) (e) (e) P=0.113 | |LOGISTIC REGRESSION| P=0.003 ** (e) (e) (e) P=0.074 | |COCH-ARM / FISHERS | P=0.003 ** (e) (e) (e) P=0.112 | |ORDER RESTRICTED | P=0.003 ** (e) (e) (e) (e) | |=================================================================================================================================| Date: 04/14/04 EXPERIMENT: 99035 TEST: 01 Page 10 Statistical Analysis of Non-neoplastic Lesions in Mice(P16(INK4A)/(+/-) (C57BL/6)) - TRANSGENIC MODEL EVALUATION II ( GLY Terminal Sacrifice at 40 weeks |=================================================================================================================================| | | | | | Males | |Dose | 0 MG/KG 25 MG/KG 50 MG/KG 100 200 | | | MG/KG MG/KG | |=================================================================================================================================| | | |Heart: Myocardium | | Degeneration | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 2/15 (13%) 0/15 (0%) 0/15 (0%) 2/15 (13%) 0/15 (0%) | |POLY-3 RATE (b) | 2/15.00 0/14.74 0/13.80 2/14.37 0/11.42 | |POLY-3 PERCENT (g) | 13.3% 0.0% 0.0% 13.9% 0.0% | |TERMINAL (d) | 0/13 (0%) 0/14 (0%) 0/13 (0%) 2/14 (14%) 0/7 (0%) | |FIRST INCIDENCE | 196 --- --- 280 (T) --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.453N P=0.232N P=0.247N P=0.680N P=0.285N | |POLY 3 | P=0.420N P=0.236N P=0.251N P=0.683 P=0.298N | |POLY 1.5 | P=0.393N P=0.234N P=0.244N P=0.689 P=0.268N | |POLY 6 | P=0.452N P=0.239N P=0.257N P=0.677 P=0.339N | |LOGISTIC REGRESSION| P=0.243N (e) P=0.121N P=0.667 P=0.049N* | |COCH-ARM / FISHERS | P=0.358N P=0.241N P=0.241N P=0.701N P=0.241N | |ORDER RESTRICTED | P=0.129N (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 MG/KG 25 MG/KG 50 MG/KG 100 200 | | | MG/KG MG/KG | |=================================================================================================================================| | | |Heart: Myocardium | | Degeneration | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/15 (0%) 0/15 (0%) 0/15 (0%) 0/15 (0%) 0/15 (0%) | |POLY-3 RATE (b) | 0/13.88 0/14.62 0/14.15 0/14.62 0/12.41 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 0/13 (0%) 0/14 (0%) 0/12 (0%) 0/14 (0%) 0/9 (0%) | |FIRST INCIDENCE | --- --- --- --- --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | (e) (e) (e) (e) (e) | |POLY 3 | (e) (e) (e) (e) (e) | |POLY 1.5 | (e) (e) (e) (e) (e) | |POLY 6 | (e) (e) (e) (e) (e) | |LOGISTIC REGRESSION| (e) (e) (e) (e) (e) | |COCH-ARM / FISHERS | (e) (e) (e) (e) (e) | |ORDER RESTRICTED | (e) (e) (e) (e) (e) | |=================================================================================================================================| Date: 04/14/04 EXPERIMENT: 99035 TEST: 01 Page 11 Statistical Analysis of Non-neoplastic Lesions in Mice(P16(INK4A)/(+/-) (C57BL/6)) - TRANSGENIC MODEL EVALUATION II ( GLY Terminal Sacrifice at 40 weeks |=================================================================================================================================| | | | | | Males | |Dose | 0 MG/KG 25 MG/KG 50 MG/KG 100 200 | | | MG/KG MG/KG | |=================================================================================================================================| | | |Heart: Myocardium | | Mineralization | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/15 (0%) 0/15 (0%) 2/15 (13%) 1/15 (7%) 5/15 (33%) | |POLY-3 RATE (b) | 0/13.95 0/14.74 2/14.66 1/14.37 5/13.21 | |POLY-3 PERCENT (g) | 0.0% 0.0% 13.6% 7.0% 37.9% | |TERMINAL (d) | 0/13 (0%) 0/14 (0%) 1/13 (8%) 1/14 (7%) 0/7 (0%) | |FIRST INCIDENCE | --- --- 146 280 (T) 208 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P<0.001 ** (e) P=0.240 P=0.515 P=0.019 * | |POLY 3 | P<0.001 ** (e) P=0.243 P=0.506 P=0.012 * | |POLY 1.5 | P<0.001 ** (e) P=0.238 P=0.503 P=0.014 * | |POLY 6 | P<0.001 ** (e) P=0.247 P=0.509 P=0.011 * | |LOGISTIC REGRESSION| P=0.015 * (e) P=0.292 P=0.515 P=0.054 | |COCH-ARM / FISHERS | P=0.002 ** (e) P=0.241 P=0.500 P=0.021 * | |ORDER RESTRICTED | P<0.001 ** (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 MG/KG 25 MG/KG 50 MG/KG 100 200 | | | MG/KG MG/KG | |=================================================================================================================================| | | |Heart: Myocardium | | Mineralization | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 1/15 (7%) 0/15 (0%) 0/15 (0%) 0/15 (0%) 0/15 (0%) | |POLY-3 RATE (b) | 1/13.88 0/14.62 0/14.15 0/14.62 0/12.41 | |POLY-3 PERCENT (g) | 7.2% 0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 1/13 (8%) 0/14 (0%) 0/12 (0%) 0/14 (0%) 0/9 (0%) | |FIRST INCIDENCE | 281 (T) --- --- --- --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.397N P=0.485N P=0.516N P=0.485N P=0.573N | |POLY 3 | P=0.342N P=0.490N P=0.496N P=0.490N P=0.522N | |POLY 1.5 | P=0.353N P=0.490N P=0.494N P=0.490N P=0.512N | |POLY 6 | P=0.329N P=0.491N P=0.501N P=0.491N P=0.534N | |LOGISTIC REGRESSION| P=0.397N (e) (e) (e) (e) | |COCH-ARM / FISHERS | P=0.361N P=0.500N P=0.500N P=0.500N P=0.500N | |ORDER RESTRICTED | P=0.107N (e) (e) (e) (e) | |=================================================================================================================================| Date: 04/14/04 EXPERIMENT: 99035 TEST: 01 Page 12 Statistical Analysis of Non-neoplastic Lesions in Mice(P16(INK4A)/(+/-) (C57BL/6)) - TRANSGENIC MODEL EVALUATION II ( GLY Terminal Sacrifice at 40 weeks |=================================================================================================================================| | | | | | Males | |Dose | 0 MG/KG 25 MG/KG 50 MG/KG 100 200 | | | MG/KG MG/KG | |=================================================================================================================================| | | |Heart: Myocardium | | Necrosis | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/15 (0%) 0/15 (0%) 0/15 (0%) 0/15 (0%) 2/15 (13%) | |POLY-3 RATE (b) | 0/13.95 0/14.74 0/13.80 0/14.37 2/11.66 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 0.0% 17.2% | |TERMINAL (d) | 0/13 (0%) 0/14 (0%) 0/13 (0%) 0/14 (0%) 0/7 (0%) | |FIRST INCIDENCE | --- --- --- --- 260 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.007 ** (e) (e) (e) P=0.152 | |POLY 3 | P=0.016 * (e) (e) (e) P=0.190 | |POLY 1.5 | P=0.017 * (e) (e) (e) P=0.207 | |POLY 6 | P=0.015 * (e) (e) (e) P=0.171 | |LOGISTIC REGRESSION| P=0.018 * (e) (e) (e) P=0.189 | |COCH-ARM / FISHERS | P=0.021 * (e) (e) (e) P=0.241 | |ORDER RESTRICTED | P=0.008 ** (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 MG/KG 25 MG/KG 50 MG/KG 100 200 | | | MG/KG MG/KG | |=================================================================================================================================| | | |Heart: Myocardium | | Necrosis | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/15 (0%) 0/15 (0%) 0/15 (0%) 0/15 (0%) 0/15 (0%) | |POLY-3 RATE (b) | 0/13.88 0/14.62 0/14.15 0/14.62 0/12.41 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 0/13 (0%) 0/14 (0%) 0/12 (0%) 0/14 (0%) 0/9 (0%) | |FIRST INCIDENCE | --- --- --- --- --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | (e) (e) (e) (e) (e) | |POLY 3 | (e) (e) (e) (e) (e) | |POLY 1.5 | (e) (e) (e) (e) (e) | |POLY 6 | (e) (e) (e) (e) (e) | |LOGISTIC REGRESSION| (e) (e) (e) (e) (e) | |COCH-ARM / FISHERS | (e) (e) (e) (e) (e) | |ORDER RESTRICTED | (e) (e) (e) (e) (e) | |=================================================================================================================================| Date: 04/14/04 EXPERIMENT: 99035 TEST: 01 Page 13 Statistical Analysis of Non-neoplastic Lesions in Mice(P16(INK4A)/(+/-) (C57BL/6)) - TRANSGENIC MODEL EVALUATION II ( GLY Terminal Sacrifice at 40 weeks |=================================================================================================================================| | | | | | Males | |Dose | 0 MG/KG 25 MG/KG 50 MG/KG 100 200 | | | MG/KG MG/KG | |=================================================================================================================================| | | |Kidney | | Nephropathy | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 4/15 (27%) 5/15 (33%) 5/15 (33%) 4/15 (27%) 4/15 (27%) | |POLY-3 RATE (b) | 4/13.95 5/15.00 5/13.80 4/14.37 4/11.42 | |POLY-3 PERCENT (g) | 28.7% 33.3% 36.2% 27.8% 35.0% | |TERMINAL (d) | 4/13 (31%) 4/14 (29%) 5/13 (39%) 4/14 (29%) 4/7 (57%) | |FIRST INCIDENCE | 280 (T) 253 280 (T) 280 (T) 280 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.261 P=0.556 P=0.500 P=0.615N P=0.257 | |POLY 3 | P=0.512 P=0.551 P=0.493 P=0.639N P=0.534 | |POLY 1.5 | P=0.549N P=0.530 P=0.491 P=0.647N P=0.590 | |POLY 6 | P=0.432 P=0.574 P=0.499 P=0.629N P=0.455 | |LOGISTIC REGRESSION| P=0.380 P=0.534 P=0.500 P=0.615N P=0.257 | |COCH-ARM / FISHERS | P=0.464N P=0.500 P=0.500 P=0.659N P=0.659N | |ORDER RESTRICTED | P=0.638 (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 MG/KG 25 MG/KG 50 MG/KG 100 200 | | | MG/KG MG/KG | |=================================================================================================================================| | | |Kidney | | Nephropathy | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 12/15 (80%) 12/15 (80%) 10/15 (67%) 14/15 (93%) 9/15 (60%) | |POLY-3 RATE (b) | 12/14.86 12/15.00 10/14.15 14/15.00 9/13.49 | |POLY-3 PERCENT (g) | 80.8% 80.0% 70.7% 93.3% 66.7% | |TERMINAL (d) | 11/13 (85%) 11/14 (79%) 10/12 (83%) 13/14 (93%) 6/9 (67%) | |FIRST INCIDENCE | 83 239 281 (T) 239 186 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.347 P=0.524N P=0.470N P=0.486 P=0.605 | |POLY 3 | P=0.348N P=0.655N P=0.420N P=0.317 P=0.336N | |POLY 1.5 | P=0.298N P=0.662N P=0.384N P=0.308 P=0.294N | |POLY 6 | P=0.378N P=0.640N P=0.472N P=0.334 P=0.364N | |LOGISTIC REGRESSION| P=0.245N P=0.654 P=0.326N P=0.280 P=0.226N | |COCH-ARM / FISHERS | P=0.195N P=0.674N P=0.341N P=0.299 P=0.213N | |ORDER RESTRICTED | P=0.292N (e) (e) (e) (e) | |=================================================================================================================================| Date: 04/14/04 EXPERIMENT: 99035 TEST: 01 Page 14 Statistical Analysis of Non-neoplastic Lesions in Mice(P16(INK4A)/(+/-) (C57BL/6)) - TRANSGENIC MODEL EVALUATION II ( GLY Terminal Sacrifice at 40 weeks |=================================================================================================================================| | | | | | Males | |Dose | 0 MG/KG 25 MG/KG 50 MG/KG 100 200 | | | MG/KG MG/KG | |=================================================================================================================================| | | |Kidney: Renal Tubule | | Accumulation, Hyaline Droplet | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/15 (0%) 0/15 (0%) 1/15 (7%) 0/15 (0%) 1/15 (7%) | |POLY-3 RATE (b) | 0/13.95 0/14.74 1/14.14 0/14.37 1/11.62 | |POLY-3 PERCENT (g) | 0.0% 0.0% 7.1% 0.0% 8.6% | |TERMINAL (d) | 0/13 (0%) 0/14 (0%) 0/13 (0%) 0/14 (0%) 0/7 (0%) | |FIRST INCIDENCE | --- --- 244 --- 260 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.228 (e) P=0.515 (e) P=0.427 | |POLY 3 | P=0.263 (e) P=0.503 (e) P=0.464 | |POLY 1.5 | P=0.281 (e) P=0.500 (e) P=0.479 | |POLY 6 | P=0.244 (e) P=0.508 (e) P=0.444 | |LOGISTIC REGRESSION| P=0.382 (e) P=0.538 (e) P=0.506 | |COCH-ARM / FISHERS | P=0.306 (e) P=0.500 (e) P=0.500 | |ORDER RESTRICTED | P=0.185 (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 MG/KG 25 MG/KG 50 MG/KG 100 200 | | | MG/KG MG/KG | |=================================================================================================================================| | | |Kidney: Renal Tubule | | Accumulation, Hyaline Droplet | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/15 (0%) 0/15 (0%) 2/15 (13%) 1/15 (7%) 3/15 (20%) | |POLY-3 RATE (b) | 0/13.88 0/14.62 2/14.59 1/14.62 3/13.48 | |POLY-3 PERCENT (g) | 0.0% 0.0% 13.7% 6.8% 22.3% | |TERMINAL (d) | 0/13 (0%) 0/14 (0%) 1/12 (8%) 1/14 (7%) 0/9 (0%) | |FIRST INCIDENCE | --- --- 232 281 (T) 186 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.022 * (e) P=0.238 P=0.515 P=0.100 | |POLY 3 | P=0.030 * (e) P=0.243 P=0.510 P=0.099 | |POLY 1.5 | P=0.032 * (e) P=0.242 P=0.510 P=0.103 | |POLY 6 | P=0.029 * (e) P=0.241 P=0.509 P=0.096 | |LOGISTIC REGRESSION| P=0.054 (e) P=0.201 P=0.515 P=0.117 | |COCH-ARM / FISHERS | P=0.035 * (e) P=0.241 P=0.500 P=0.112 | |ORDER RESTRICTED | P=0.026 * (e) (e) (e) (e) | |=================================================================================================================================| Date: 04/14/04 EXPERIMENT: 99035 TEST: 01 Page 15 Statistical Analysis of Non-neoplastic Lesions in Mice(P16(INK4A)/(+/-) (C57BL/6)) - TRANSGENIC MODEL EVALUATION II ( GLY Terminal Sacrifice at 40 weeks |=================================================================================================================================| | | | | | Males | |Dose | 0 MG/KG 25 MG/KG 50 MG/KG 100 200 | | | MG/KG MG/KG | |=================================================================================================================================| | | |Liver | | Angiectasis Focal | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/15 (0%) 0/15 (0%) 0/15 (0%) 0/15 (0%) 1/15 (7%) | |POLY-3 RATE (b) | 0/13.95 0/14.74 0/13.80 0/14.37 1/11.42 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 0.0% 8.8% | |TERMINAL (d) | 0/13 (0%) 0/14 (0%) 0/13 (0%) 0/14 (0%) 1/7 (14%) | |FIRST INCIDENCE | --- --- --- --- 280 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.074 (e) (e) (e) P=0.377 | |POLY 3 | P=0.123 (e) (e) (e) P=0.460 | |POLY 1.5 | P=0.132 (e) (e) (e) P=0.478 | |POLY 6 | P=0.114 (e) (e) (e) P=0.437 | |LOGISTIC REGRESSION| (e) (e) (e) (e) P=0.377 | |COCH-ARM / FISHERS | P=0.143 (e) (e) (e) P=0.500 | |ORDER RESTRICTED | P=0.061 (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 MG/KG 25 MG/KG 50 MG/KG 100 200 | | | MG/KG MG/KG | |=================================================================================================================================| | | |Liver | | Angiectasis Focal | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/15 (0%) 0/15 (0%) 0/15 (0%) 1/15 (7%) 2/15 (13%) | |POLY-3 RATE (b) | 0/13.88 0/14.62 0/14.15 1/14.62 2/12.44 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 6.8% 16.1% | |TERMINAL (d) | 0/13 (0%) 0/14 (0%) 0/12 (0%) 1/14 (7%) 1/9 (11%) | |FIRST INCIDENCE | --- --- --- 281 (T) 278 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.015 * (e) (e) P=0.515 P=0.183 | |POLY 3 | P=0.023 * (e) (e) P=0.510 P=0.205 | |POLY 1.5 | P=0.025 * (e) (e) P=0.510 P=0.217 | |POLY 6 | P=0.021 * (e) (e) P=0.509 P=0.194 | |LOGISTIC REGRESSION| P=0.018 * (e) (e) P=0.515 P=0.188 | |COCH-ARM / FISHERS | P=0.030 * (e) (e) P=0.500 P=0.241 | |ORDER RESTRICTED | P=0.033 * (e) (e) (e) (e) | |=================================================================================================================================| Date: 04/14/04 EXPERIMENT: 99035 TEST: 01 Page 16 Statistical Analysis of Non-neoplastic Lesions in Mice(P16(INK4A)/(+/-) (C57BL/6)) - TRANSGENIC MODEL EVALUATION II ( GLY Terminal Sacrifice at 40 weeks |=================================================================================================================================| | | | | | Males | |Dose | 0 MG/KG 25 MG/KG 50 MG/KG 100 200 | | | MG/KG MG/KG | |=================================================================================================================================| | | |Liver | | Hematopoietic Cell Proliferation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/15 (0%) 1/15 (7%) 0/15 (0%) 2/15 (13%) 1/15 (7%) | |POLY-3 RATE (b) | 0/13.95 1/14.74 0/13.80 2/14.37 1/11.95 | |POLY-3 PERCENT (g) | 0.0% 6.8% 0.0% 13.9% 8.4% | |TERMINAL (d) | 0/13 (0%) 1/14 (7%) 0/13 (0%) 2/14 (14%) 0/7 (0%) | |FIRST INCIDENCE | --- 280 (T) --- 280 (T) 217 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.171 P=0.515 (e) P=0.252 P=0.469 | |POLY 3 | P=0.224 P=0.511 (e) P=0.238 P=0.469 | |POLY 1.5 | P=0.254 P=0.507 (e) P=0.235 P=0.482 | |POLY 6 | P=0.190 P=0.515 (e) P=0.242 P=0.452 | |LOGISTIC REGRESSION| P=0.322 P=0.515 (e) P=0.252 P=0.688 | |COCH-ARM / FISHERS | P=0.293 P=0.500 (e) P=0.241 P=0.500 | |ORDER RESTRICTED | P=0.198 (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 MG/KG 25 MG/KG 50 MG/KG 100 200 | | | MG/KG MG/KG | |=================================================================================================================================| | | |Liver | | Hematopoietic Cell Proliferation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 2/15 (13%) 3/15 (20%) 1/15 (7%) 1/15 (7%) 2/15 (13%) | |POLY-3 RATE (b) | 2/13.88 3/14.62 1/14.15 1/14.62 2/12.44 | |POLY-3 PERCENT (g) | 14.4% 20.5% 7.1% 6.8% 16.1% | |TERMINAL (d) | 2/13 (15%) 3/14 (21%) 1/12 (8%) 1/14 (7%) 1/9 (11%) | |FIRST INCIDENCE | 281 (T) 281 (T) 281 (T) 281 (T) 278 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.567 P=0.536 P=0.529N P=0.473N P=0.577 | |POLY 3 | P=0.521N P=0.524 P=0.493N P=0.482N P=0.659 | |POLY 1.5 | P=0.512N P=0.523 P=0.489N P=0.483N P=0.679 | |POLY 6 | P=0.528N P=0.522 P=0.502N P=0.484N P=0.638 | |LOGISTIC REGRESSION| P=0.596N P=0.536 P=0.529N P=0.473N P=0.626 | |COCH-ARM / FISHERS | P=0.500N P=0.500 P=0.500N P=0.500N P=0.701N | |ORDER RESTRICTED | P=0.494N (e) (e) (e) (e) | |=================================================================================================================================| Date: 04/14/04 EXPERIMENT: 99035 TEST: 01 Page 17 Statistical Analysis of Non-neoplastic Lesions in Mice(P16(INK4A)/(+/-) (C57BL/6)) - TRANSGENIC MODEL EVALUATION II ( GLY Terminal Sacrifice at 40 weeks |=================================================================================================================================| | | | | | Males | |Dose | 0 MG/KG 25 MG/KG 50 MG/KG 100 200 | | | MG/KG MG/KG | |=================================================================================================================================| | | |Liver | | Infiltration Cellular Lymphoid | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 1/15 (7%) 2/15 (13%) 0/15 (0%) 2/15 (13%) 1/15 (7%) | |POLY-3 RATE (b) | 1/14.34 2/14.74 0/13.80 2/14.37 1/11.42 | |POLY-3 PERCENT (g) | 7.0% 13.6% 0.0% 13.9% 8.8% | |TERMINAL (d) | 0/13 (0%) 2/14 (14%) 0/13 (0%) 2/14 (14%) 1/7 (14%) | |FIRST INCIDENCE | 237 280 (T) --- 280 (T) 280 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.441 P=0.525 P=0.500N P=0.517 P=0.651 | |POLY 3 | P=0.514 P=0.510 P=0.508N P=0.501 P=0.708 | |POLY 1.5 | P=0.560 P=0.507 P=0.505N P=0.501 P=0.732 | |POLY 6 | P=0.456 P=0.511 P=0.510N P=0.500 P=0.674 | |LOGISTIC REGRESSION| P=0.580 P=0.414 P=0.448N P=0.483 P=0.768N | |COCH-ARM / FISHERS | P=0.618 P=0.500 P=0.500N P=0.500 P=0.759N | |ORDER RESTRICTED | P=0.596 (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 MG/KG 25 MG/KG 50 MG/KG 100 200 | | | MG/KG MG/KG | |=================================================================================================================================| | | |Liver | | Infiltration Cellular Lymphoid | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/15 (0%) 3/15 (20%) 1/15 (7%) 1/15 (7%) 1/15 (7%) | |POLY-3 RATE (b) | 0/13.88 3/14.62 1/14.15 1/14.62 1/12.41 | |POLY-3 PERCENT (g) | 0.0% 20.5% 7.1% 6.8% 8.1% | |TERMINAL (d) | 0/13 (0%) 3/14 (21%) 1/12 (8%) 1/14 (7%) 1/9 (11%) | |FIRST INCIDENCE | --- 281 (T) 281 (T) 281 (T) 281 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.569 P=0.128 P=0.484 P=0.515 P=0.427 | |POLY 3 | P=0.581N P=0.115 P=0.504 P=0.510 P=0.478 | |POLY 1.5 | P=0.569N P=0.115 P=0.506 P=0.510 P=0.488 | |POLY 6 | P=0.593N P=0.114 P=0.499 P=0.509 P=0.466 | |LOGISTIC REGRESSION| (e) P=0.128 P=0.484 P=0.515 P=0.427 | |COCH-ARM / FISHERS | P=0.560N P=0.112 P=0.500 P=0.500 P=0.500 | |ORDER RESTRICTED | P=0.295 (e) (e) (e) (e) | |=================================================================================================================================| Date: 04/14/04 EXPERIMENT: 99035 TEST: 01 Page 18 Statistical Analysis of Non-neoplastic Lesions in Mice(P16(INK4A)/(+/-) (C57BL/6)) - TRANSGENIC MODEL EVALUATION II ( GLY Terminal Sacrifice at 40 weeks |=================================================================================================================================| | | | | | Males | |Dose | 0 MG/KG 25 MG/KG 50 MG/KG 100 200 | | | MG/KG MG/KG | |=================================================================================================================================| | | |Liver | | Inflammation Chronic | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 6/15 (40%) 9/15 (60%) 8/15 (53%) 9/15 (60%) 2/15 (13%) | |POLY-3 RATE (b) | 6/13.95 9/14.74 8/13.80 9/15.00 2/11.95 | |POLY-3 PERCENT (g) | 43.0% 61.1% 58.0% 60.0% 16.7% | |TERMINAL (d) | 6/13 (46%) 9/14 (64%) 8/13 (62%) 8/14 (57%) 1/7 (14%) | |FIRST INCIDENCE | 280 (T) 280 (T) 280 (T) 201 217 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.263N P=0.291 P=0.350 P=0.304 P=0.361N | |POLY 3 | P=0.070N P=0.278 P=0.343 P=0.296 P=0.152N | |POLY 1.5 | P=0.046N* P=0.261 P=0.344 P=0.270 P=0.129N | |POLY 6 | P=0.111N P=0.295 P=0.350 P=0.329 P=0.188N | |LOGISTIC REGRESSION| P=0.084N P=0.291 P=0.350 P=0.241 P=0.185N | |COCH-ARM / FISHERS | P=0.030N* P=0.233 P=0.358 P=0.233 P=0.107N | |ORDER RESTRICTED | P=0.036N* (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 MG/KG 25 MG/KG 50 MG/KG 100 200 | | | MG/KG MG/KG | |=================================================================================================================================| | | |Liver | | Inflammation Chronic | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 11/15 (73%) 10/15 (67%) 8/15 (53%) 8/15 (53%) 7/15 (47%) | |POLY-3 RATE (b) | 11/13.88 10/15.00 8/14.15 8/14.62 7/12.44 | |POLY-3 PERCENT (g) | 79.2% 66.7% 56.5% 54.7% 56.3% | |TERMINAL (d) | 11/13 (85%) 9/14 (64%) 8/12 (67%) 8/14 (57%) 6/9 (67%) | |FIRST INCIDENCE | 281 (T) 239 281 (T) 281 (T) 278 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.418N P=0.379N P=0.285N P=0.132N P=0.531N | |POLY 3 | P=0.167N P=0.370N P=0.184N P=0.158N P=0.191N | |POLY 1.5 | P=0.132N P=0.394N P=0.179N P=0.165N P=0.149N | |POLY 6 | P=0.207N P=0.351N P=0.206N P=0.160N P=0.248N | |LOGISTIC REGRESSION| P=0.232N P=0.410N P=0.285N P=0.132N P=0.307N | |COCH-ARM / FISHERS | P=0.092N P=0.500N P=0.225N P=0.225N P=0.132N | |ORDER RESTRICTED | P=0.184N (e) (e) (e) (e) | |=================================================================================================================================| Date: 04/14/04 EXPERIMENT: 99035 TEST: 01 Page 19 Statistical Analysis of Non-neoplastic Lesions in Mice(P16(INK4A)/(+/-) (C57BL/6)) - TRANSGENIC MODEL EVALUATION II ( GLY Terminal Sacrifice at 40 weeks |=================================================================================================================================| | | | | | Males | |Dose | 0 MG/KG 25 MG/KG 50 MG/KG 100 200 | | | MG/KG MG/KG | |=================================================================================================================================| | | |Liver | | Necrosis Focal | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 1/15 (7%) 2/15 (13%) 2/15 (13%) 0/15 (0%) 5/15 (33%) | |POLY-3 RATE (b) | 1/14.61 2/15.00 2/15.00 0/14.37 5/13.56 | |POLY-3 PERCENT (g) | 6.9% 13.3% 13.3% 0.0% 36.9% | |TERMINAL (d) | 0/13 (0%) 1/14 (7%) 0/13 (0%) 0/14 (0%) 0/7 (0%) | |FIRST INCIDENCE | 196 253 146 --- 181 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.028 * P=0.525 P=0.501 P=0.500N P=0.075 | |POLY 3 | P=0.035 * P=0.509 P=0.509 P=0.503N P=0.062 | |POLY 1.5 | P=0.038 * P=0.505 P=0.505 P=0.502N P=0.069 | |POLY 6 | P=0.033 * P=0.515 P=0.515 P=0.503N P=0.054 | |LOGISTIC REGRESSION| P=0.452 P=0.170 P=0.381 (e) P=0.349 | |COCH-ARM / FISHERS | P=0.046 * P=0.500 P=0.500 P=0.500N P=0.084 | |ORDER RESTRICTED | P=0.013 * (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 MG/KG 25 MG/KG 50 MG/KG 100 200 | | | MG/KG MG/KG | |=================================================================================================================================| | | |Liver | | Necrosis Focal | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/15 (0%) 0/15 (0%) 5/15 (33%) 2/15 (13%) 2/15 (13%) | |POLY-3 RATE (b) | 0/13.88 0/14.62 5/14.98 2/14.62 2/13.46 | |POLY-3 PERCENT (g) | 0.0% 0.0% 33.4% 13.7% 14.9% | |TERMINAL (d) | 0/13 (0%) 0/14 (0%) 3/12 (25%) 2/14 (14%) 0/9 (0%) | |FIRST INCIDENCE | --- --- 232 281 (T) 186 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.182 (e) P=0.030 * P=0.252 P=0.223 | |POLY 3 | P=0.231 (e) P=0.022 * P=0.243 P=0.223 | |POLY 1.5 | P=0.243 (e) P=0.021 * P=0.243 P=0.228 | |POLY 6 | P=0.223 (e) P=0.023 * P=0.242 P=0.219 | |LOGISTIC REGRESSION| P=0.324 (e) P=0.019 * P=0.252 P=0.231 | |COCH-ARM / FISHERS | P=0.265 (e) P=0.021 * P=0.241 P=0.241 | |ORDER RESTRICTED | P=0.070 (e) (e) (e) (e) | |=================================================================================================================================| Date: 04/14/04 EXPERIMENT: 99035 TEST: 01 Page 20 Statistical Analysis of Non-neoplastic Lesions in Mice(P16(INK4A)/(+/-) (C57BL/6)) - TRANSGENIC MODEL EVALUATION II ( GLY Terminal Sacrifice at 40 weeks |=================================================================================================================================| | | | | | Males | |Dose | 0 MG/KG 25 MG/KG 50 MG/KG 100 200 | | | MG/KG MG/KG | |=================================================================================================================================| | | |Lung | | Inflammation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 3/15 (20%) 7/15 (47%) 5/15 (33%) 4/15 (27%) 2/15 (13%) | |POLY-3 RATE (b) | 3/13.95 7/14.74 5/13.80 4/14.37 2/11.42 | |POLY-3 PERCENT (g) | 21.5% 47.5% 36.2% 27.8% 17.5% | |TERMINAL (d) | 3/13 (23%) 7/14 (50%) 5/13 (39%) 4/14 (29%) 2/7 (29%) | |FIRST INCIDENCE | 280 (T) 280 (T) 280 (T) 280 (T) 280 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.442N P=0.152 P=0.338 P=0.545 P=0.604 | |POLY 3 | P=0.230N P=0.141 P=0.334 P=0.518 P=0.596N | |POLY 1.5 | P=0.187N P=0.133 P=0.334 P=0.510 P=0.554N | |POLY 6 | P=0.287N P=0.149 P=0.338 P=0.528 P=0.650N | |LOGISTIC REGRESSION| P=0.442N P=0.152 P=0.338 P=0.545 P=0.604 | |COCH-ARM / FISHERS | P=0.138N P=0.123 P=0.341 P=0.500 P=0.500N | |ORDER RESTRICTED | P=0.307N (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 MG/KG 25 MG/KG 50 MG/KG 100 200 | | | MG/KG MG/KG | |=================================================================================================================================| | | |Lung | | Inflammation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 8/15 (53%) 8/15 (53%) 7/15 (47%) 5/15 (33%) 3/15 (20%) | |POLY-3 RATE (b) | 8/13.88 8/15.00 7/14.15 5/14.62 3/12.44 | |POLY-3 PERCENT (g) | 57.6% 53.3% 49.5% 34.2% 24.1% | |TERMINAL (d) | 8/13 (62%) 7/14 (50%) 7/12 (58%) 5/14 (36%) 2/9 (22%) | |FIRST INCIDENCE | 281 (T) 239 281 (T) 281 (T) 278 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.081N P=0.558N P=0.595N P=0.174N P=0.206N | |POLY 3 | P=0.033N* P=0.555N P=0.479N P=0.191N P=0.083N | |POLY 1.5 | P=0.026N* P=0.571N P=0.467N P=0.194N P=0.068N | |POLY 6 | P=0.042N* P=0.543N P=0.508N P=0.193N P=0.102N | |LOGISTIC REGRESSION| P=0.040N* P=0.592N P=0.595N P=0.174N P=0.125N | |COCH-ARM / FISHERS | P=0.019N* P=0.642N P=0.500N P=0.231N P=0.064N | |ORDER RESTRICTED | P=0.070N (e) (e) (e) (e) | |=================================================================================================================================| Date: 04/14/04 EXPERIMENT: 99035 TEST: 01 Page 21 Statistical Analysis of Non-neoplastic Lesions in Mice(P16(INK4A)/(+/-) (C57BL/6)) - TRANSGENIC MODEL EVALUATION II ( GLY Terminal Sacrifice at 40 weeks |=================================================================================================================================| | | | | | Males | |Dose | 0 MG/KG 25 MG/KG 50 MG/KG 100 200 | | | MG/KG MG/KG | |=================================================================================================================================| | | |Lung: Alveolar Epithelium | | Hyperplasia Focal | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/15 (0%) 2/15 (13%) 0/15 (0%) 2/15 (13%) 2/15 (13%) | |POLY-3 RATE (b) | 0/13.95 2/14.74 0/13.80 2/14.37 2/11.42 | |POLY-3 PERCENT (g) | 0.0% 13.6% 0.0% 13.9% 17.5% | |TERMINAL (d) | 0/13 (0%) 2/14 (14%) 0/13 (0%) 2/14 (14%) 2/7 (29%) | |FIRST INCIDENCE | --- 280 (T) --- 280 (T) 280 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.056 P=0.252 (e) P=0.252 P=0.112 | |POLY 3 | P=0.128 P=0.244 (e) P=0.238 P=0.186 | |POLY 1.5 | P=0.150 P=0.239 (e) P=0.235 P=0.205 | |POLY 6 | P=0.103 P=0.249 (e) P=0.242 P=0.163 | |LOGISTIC REGRESSION| (e) P=0.252 (e) P=0.252 P=0.112 | |COCH-ARM / FISHERS | P=0.183 P=0.241 (e) P=0.241 P=0.241 | |ORDER RESTRICTED | P=0.110 (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 MG/KG 25 MG/KG 50 MG/KG 100 200 | | | MG/KG MG/KG | |=================================================================================================================================| | | |Lung: Alveolar Epithelium | | Hyperplasia Focal | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 1/15 (7%) 2/15 (13%) 1/15 (7%) 0/15 (0%) 1/15 (7%) | |POLY-3 RATE (b) | 1/13.88 2/14.62 1/14.15 0/14.62 1/12.41 | |POLY-3 PERCENT (g) | 7.2% 13.7% 7.1% 0.0% 8.1% | |TERMINAL (d) | 1/13 (8%) 2/14 (14%) 1/12 (8%) 0/14 (0%) 1/9 (11%) | |FIRST INCIDENCE | 281 (T) 281 (T) 281 (T) --- 281 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.544N P=0.527 P=0.747 P=0.485N P=0.680 | |POLY 3 | P=0.437N P=0.518 P=0.757N P=0.490N P=0.736 | |POLY 1.5 | P=0.435N P=0.517 P=0.754N P=0.490N P=0.748 | |POLY 6 | P=0.438N P=0.516 P=0.760 P=0.491N P=0.722 | |LOGISTIC REGRESSION| P=0.544N P=0.527 P=0.747 (e) P=0.680 | |COCH-ARM / FISHERS | P=0.435N P=0.500 P=0.759N P=0.500N P=0.759N | |ORDER RESTRICTED | P=0.452N (e) (e) (e) (e) | |=================================================================================================================================| Date: 04/14/04 EXPERIMENT: 99035 TEST: 01 Page 22 Statistical Analysis of Non-neoplastic Lesions in Mice(P16(INK4A)/(+/-) (C57BL/6)) - TRANSGENIC MODEL EVALUATION II ( GLY Terminal Sacrifice at 40 weeks |=================================================================================================================================| | | | | | Males | |Dose | 0 MG/KG 25 MG/KG 50 MG/KG 100 200 | | | MG/KG MG/KG | |=================================================================================================================================| | | |Lymph Node, Mandibular | | Hyperplasia Lymphoid | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/15 (0%) 2/15 (13%) 0/15 (0%) 1/15 (7%) 0/15 (0%) | |POLY-3 RATE (b) | 0/13.95 2/14.74 0/13.80 1/14.37 0/11.42 | |POLY-3 PERCENT (g) | 0.0% 13.6% 0.0% 7.0% 0.0% | |TERMINAL (d) | 0/13 (0%) 2/14 (14%) 0/13 (0%) 1/14 (7%) 0/7 (0%) | |FIRST INCIDENCE | --- 280 (T) --- 280 (T) --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.551N P=0.252 (e) P=0.515 (e) | |POLY 3 | P=0.450N P=0.244 (e) P=0.506 (e) | |POLY 1.5 | P=0.436N P=0.239 (e) P=0.503 (e) | |POLY 6 | P=0.467N P=0.249 (e) P=0.509 (e) | |LOGISTIC REGRESSION| (e) P=0.252 (e) P=0.515 (e) | |COCH-ARM / FISHERS | P=0.417N P=0.241 (e) P=0.500 (e) | |ORDER RESTRICTED | P=0.360N (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 MG/KG 25 MG/KG 50 MG/KG 100 200 | | | MG/KG MG/KG | |=================================================================================================================================| | | |Lymph Node, Mandibular | | Hyperplasia Lymphoid | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 1/15 (7%) 0/15 (0%) 0/15 (0%) 0/15 (0%) 1/15 (7%) | |POLY-3 RATE (b) | 1/13.88 0/14.62 0/14.15 0/14.62 1/12.41 | |POLY-3 PERCENT (g) | 7.2% 0.0% 0.0% 0.0% 8.1% | |TERMINAL (d) | 1/13 (8%) 0/14 (0%) 0/12 (0%) 0/14 (0%) 1/9 (11%) | |FIRST INCIDENCE | 281 (T) --- --- --- 281 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.430 P=0.485N P=0.516N P=0.485N P=0.680 | |POLY 3 | P=0.478 P=0.490N P=0.496N P=0.490N P=0.736 | |POLY 1.5 | P=0.484 P=0.490N P=0.494N P=0.490N P=0.748 | |POLY 6 | P=0.474 P=0.491N P=0.501N P=0.491N P=0.722 | |LOGISTIC REGRESSION| P=0.430 (e) (e) (e) P=0.680 | |COCH-ARM / FISHERS | P=0.500 P=0.500N P=0.500N P=0.500N P=0.759N | |ORDER RESTRICTED | P=0.305 (e) (e) (e) (e) | |=================================================================================================================================| Date: 04/14/04 EXPERIMENT: 99035 TEST: 01 Page 23 Statistical Analysis of Non-neoplastic Lesions in Mice(P16(INK4A)/(+/-) (C57BL/6)) - TRANSGENIC MODEL EVALUATION II ( GLY Terminal Sacrifice at 40 weeks |=================================================================================================================================| | | | | | Males | |Dose | 0 MG/KG 25 MG/KG 50 MG/KG 100 200 | | | MG/KG MG/KG | |=================================================================================================================================| | | |Lymph Node, Mesenteric | | Hyperplasia Lymphoid | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/15 (0%) 2/15 (13%) 0/15 (0%) 1/14 (7%) 1/15 (7%) | |POLY-3 RATE (b) | 0/13.95 2/14.74 0/13.80 1/14.00 1/11.42 | |POLY-3 PERCENT (g) | 0.0% 13.6% 0.0% 7.1% 8.8% | |TERMINAL (d) | 0/13 (0%) 2/14 (14%) 0/13 (0%) 1/14 (7%) 1/7 (14%) | |FIRST INCIDENCE | --- 280 (T) --- 280 (T) 280 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.334 P=0.252 (e) P=0.515 P=0.377 | |POLY 3 | P=0.424 P=0.244 (e) P=0.501 P=0.460 | |POLY 1.5 | P=0.455 P=0.239 (e) P=0.495 P=0.478 | |POLY 6 | P=0.385 P=0.249 (e) P=0.507 P=0.437 | |LOGISTIC REGRESSION| (e) P=0.252 (e) P=0.515 P=0.377 | |COCH-ARM / FISHERS | P=0.496 P=0.241 (e) P=0.483 P=0.500 | |ORDER RESTRICTED | P=0.326 (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 MG/KG 25 MG/KG 50 MG/KG 100 200 | | | MG/KG MG/KG | |=================================================================================================================================| | | |Lymph Node, Mesenteric | | Hyperplasia Lymphoid | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/15 (0%) 0/15 (0%) 0/15 (0%) 1/15 (7%) 0/15 (0%) | |POLY-3 RATE (b) | 0/13.88 0/14.62 0/14.15 1/14.62 0/12.41 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 6.8% 0.0% | |TERMINAL (d) | 0/13 (0%) 0/14 (0%) 0/12 (0%) 1/14 (7%) 0/9 (0%) | |FIRST INCIDENCE | --- --- --- 281 (T) --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.603 (e) (e) P=0.515 (e) | |POLY 3 | P=0.560 (e) (e) P=0.510 (e) | |POLY 1.5 | P=0.591 (e) (e) P=0.510 (e) | |POLY 6 | P=0.529 (e) (e) P=0.509 (e) | |LOGISTIC REGRESSION| (e) (e) (e) P=0.515 (e) | |COCH-ARM / FISHERS | P=0.639 (e) (e) P=0.500 (e) | |ORDER RESTRICTED | P=0.388 (e) (e) (e) (e) | |=================================================================================================================================| Date: 04/14/04 EXPERIMENT: 99035 TEST: 01 Page 24 Statistical Analysis of Non-neoplastic Lesions in Mice(P16(INK4A)/(+/-) (C57BL/6)) - TRANSGENIC MODEL EVALUATION II ( GLY Terminal Sacrifice at 40 weeks |=================================================================================================================================| | | | | | Males | |Dose | 0 MG/KG 25 MG/KG 50 MG/KG 100 200 | | | MG/KG MG/KG | |=================================================================================================================================| | | |Lymph Node: Mediastinal | | Hyperplasia Lymphoid | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/14 (0%) 1/14 (7%) 0/15 (0%) 0/13 (0%) 0/13 (0%) | |POLY-3 RATE (b) | 0/12.95 1/13.74 0/13.80 0/12.37 0/9.42 | |POLY-3 PERCENT (g) | 0.0% 7.3% 0.0% 0.0% 0.0% | |TERMINAL (d) | 0/12 (0%) 1/13 (8%) 0/13 (0%) 0/12 (0%) 0/5 (0%) | |FIRST INCIDENCE | --- 280 (T) --- --- --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.620N P=0.516 (e) (e) (e) | |POLY 3 | P=0.469N P=0.512 (e) (e) (e) | |POLY 1.5 | P=0.491N P=0.507 (e) (e) (e) | |POLY 6 | P=0.435N P=0.516 (e) (e) (e) | |LOGISTIC REGRESSION| (e) P=0.516 (e) (e) (e) | |COCH-ARM / FISHERS | P=0.515N P=0.500 (e) (e) (e) | |ORDER RESTRICTED | P=0.455N (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 MG/KG 25 MG/KG 50 MG/KG 100 200 | | | MG/KG MG/KG | |=================================================================================================================================| | | |Lymph Node: Mediastinal | | Hyperplasia Lymphoid | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 2/13 (15%) 1/15 (7%) 0/15 (0%) 0/13 (0%) 0/14 (0%) | |POLY-3 RATE (b) | 2/11.88 1/14.62 0/14.15 0/12.62 0/11.41 | |POLY-3 PERCENT (g) | 16.8% 6.8% 0.0% 0.0% 0.0% | |TERMINAL (d) | 2/11 (18%) 1/14 (7%) 0/12 (0%) 0/12 (0%) 0/8 (0%) | |FIRST INCIDENCE | 281 (T) 281 (T) --- --- --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.130N P=0.413N P=0.216N P=0.216N P=0.307N | |POLY 3 | P=0.101N P=0.426N P=0.190N P=0.216N P=0.238N | |POLY 1.5 | P=0.104N P=0.428N P=0.189N P=0.217N P=0.225N | |POLY 6 | P=0.098N P=0.428N P=0.195N P=0.217N P=0.253N | |LOGISTIC REGRESSION| P=0.130N P=0.413N (e) (e) (e) | |COCH-ARM / FISHERS | P=0.106N P=0.444N P=0.206N P=0.240N P=0.222N | |ORDER RESTRICTED | P=0.047N* (e) (e) (e) (e) | |=================================================================================================================================| Date: 04/14/04 EXPERIMENT: 99035 TEST: 01 Page 25 Statistical Analysis of Non-neoplastic Lesions in Mice(P16(INK4A)/(+/-) (C57BL/6)) - TRANSGENIC MODEL EVALUATION II ( GLY Terminal Sacrifice at 40 weeks |=================================================================================================================================| | | | | | Males | |Dose | 0 MG/KG 25 MG/KG 50 MG/KG 100 200 | | | MG/KG MG/KG | |=================================================================================================================================| | | |Ovary | | Cyst | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | | |POLY-3 RATE (b) | | |POLY-3 PERCENT (g) | | |TERMINAL (d) | | |FIRST INCIDENCE | | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | | |POLY 3 | | |POLY 1.5 | | |POLY 6 | | |LOGISTIC REGRESSION| | |COCH-ARM / FISHERS | | |ORDER RESTRICTED | | |=================================================================================================================================| | | | | | Females | |Dose | 0 MG/KG 25 MG/KG 50 MG/KG 100 200 | | | MG/KG MG/KG | |=================================================================================================================================| | | |Ovary | | Cyst | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 4/15 (27%) 0/15 (0%) 0/15 (0%) 0/15 (0%) 2/15 (13%) | |POLY-3 RATE (b) | 4/13.88 0/14.62 0/14.15 0/14.62 2/13.12 | |POLY-3 PERCENT (g) | 28.8% 0.0% 0.0% 0.0% 15.2% | |TERMINAL (d) | 4/13 (31%) 0/14 (0%) 0/12 (0%) 0/14 (0%) 1/9 (11%) | |FIRST INCIDENCE | 281 (T) --- --- --- 186 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.603N P=0.047N* P=0.064N P=0.047N* P=0.484N | |POLY 3 | P=0.504N P=0.038N* P=0.042N* P=0.038N* P=0.353N | |POLY 1.5 | P=0.508N P=0.039N* P=0.041N* P=0.039N* P=0.337N | |POLY 6 | P=0.496N P=0.039N* P=0.044N* P=0.039N* P=0.372N | |LOGISTIC REGRESSION| P=0.477N (e) (e) (e) P=0.330N | |COCH-ARM / FISHERS | P=0.500N P=0.050N P=0.050N P=0.050N P=0.326N | |ORDER RESTRICTED | P=0.011N* (e) (e) (e) (e) | |=================================================================================================================================| Date: 04/14/04 EXPERIMENT: 99035 TEST: 01 Page 26 Statistical Analysis of Non-neoplastic Lesions in Mice(P16(INK4A)/(+/-) (C57BL/6)) - TRANSGENIC MODEL EVALUATION II ( GLY Terminal Sacrifice at 40 weeks |=================================================================================================================================| | | | | | Males | |Dose | 0 MG/KG 25 MG/KG 50 MG/KG 100 200 | | | MG/KG MG/KG | |=================================================================================================================================| | | |Pituitary Gland: Pars Distalis | | Hyperplasia Focal | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/15 (0%) 0/15 (0%) 0/14 (0%) 0/15 (0%) 0/15 (0%) | |POLY-3 RATE (b) | 0/13.95 0/14.74 0/12.80 0/14.37 0/11.42 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 0/13 (0%) 0/14 (0%) 0/12 (0%) 0/14 (0%) 0/7 (0%) | |FIRST INCIDENCE | --- --- --- --- --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | (e) (e) (e) (e) (e) | |POLY 3 | (e) (e) (e) (e) (e) | |POLY 1.5 | (e) (e) (e) (e) (e) | |POLY 6 | (e) (e) (e) (e) (e) | |LOGISTIC REGRESSION| (e) (e) (e) (e) (e) | |COCH-ARM / FISHERS | (e) (e) (e) (e) (e) | |ORDER RESTRICTED | (e) (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 MG/KG 25 MG/KG 50 MG/KG 100 200 | | | MG/KG MG/KG | |=================================================================================================================================| | | |Pituitary Gland: Pars Distalis | | Hyperplasia Focal | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 1/15 (7%) 1/15 (7%) 2/15 (13%) 1/15 (7%) 0/15 (0%) | |POLY-3 RATE (b) | 1/13.88 1/14.62 2/14.15 1/14.62 0/12.41 | |POLY-3 PERCENT (g) | 7.2% 6.8% 14.1% 6.8% 0.0% | |TERMINAL (d) | 1/13 (8%) 1/14 (7%) 2/12 (17%) 1/14 (7%) 0/9 (0%) | |FIRST INCIDENCE | 281 (T) 281 (T) 281 (T) 281 (T) --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.335N P=0.748N P=0.471 P=0.748N P=0.573N | |POLY 3 | P=0.290N P=0.749N P=0.507 P=0.749N P=0.522N | |POLY 1.5 | P=0.277N P=0.750N P=0.511 P=0.750N P=0.512N | |POLY 6 | P=0.303N P=0.751N P=0.498 P=0.751N P=0.534N | |LOGISTIC REGRESSION| P=0.335N P=0.748N P=0.471 P=0.748N (e) | |COCH-ARM / FISHERS | P=0.256N P=0.759N P=0.500 P=0.759N P=0.500N | |ORDER RESTRICTED | P=0.328N (e) (e) (e) (e) | |=================================================================================================================================| Date: 04/14/04 EXPERIMENT: 99035 TEST: 01 Page 27 Statistical Analysis of Non-neoplastic Lesions in Mice(P16(INK4A)/(+/-) (C57BL/6)) - TRANSGENIC MODEL EVALUATION II ( GLY Terminal Sacrifice at 40 weeks |=================================================================================================================================| | | | | | Males | |Dose | 0 MG/KG 25 MG/KG 50 MG/KG 100 200 | | | MG/KG MG/KG | |=================================================================================================================================| | | |Spleen | | Atrophy | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/15 (0%) 0/15 (0%) 0/15 (0%) 1/15 (7%) 2/15 (13%) | |POLY-3 RATE (b) | 0/13.95 0/14.74 0/13.80 1/15.00 2/12.48 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 6.7% 16.0% | |TERMINAL (d) | 0/13 (0%) 0/14 (0%) 0/13 (0%) 0/14 (0%) 0/7 (0%) | |FIRST INCIDENCE | --- --- --- 201 217 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.023 * (e) (e) P=0.514 P=0.197 | |POLY 3 | P=0.023 * (e) (e) P=0.514 P=0.205 | |POLY 1.5 | P=0.026 * (e) (e) P=0.509 P=0.216 | |POLY 6 | P=0.020 * (e) (e) P=0.521 P=0.192 | |LOGISTIC REGRESSION| P=0.109 (e) (e) P=0.425 P=0.434 | |COCH-ARM / FISHERS | P=0.030 * (e) (e) P=0.500 P=0.241 | |ORDER RESTRICTED | P=0.033 * (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 MG/KG 25 MG/KG 50 MG/KG 100 200 | | | MG/KG MG/KG | |=================================================================================================================================| | | |Spleen | | Atrophy | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/15 (0%) 0/15 (0%) 0/15 (0%) 0/15 (0%) 0/15 (0%) | |POLY-3 RATE (b) | 0/13.88 0/14.62 0/14.15 0/14.62 0/12.41 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 0/13 (0%) 0/14 (0%) 0/12 (0%) 0/14 (0%) 0/9 (0%) | |FIRST INCIDENCE | --- --- --- --- --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | (e) (e) (e) (e) (e) | |POLY 3 | (e) (e) (e) (e) (e) | |POLY 1.5 | (e) (e) (e) (e) (e) | |POLY 6 | (e) (e) (e) (e) (e) | |LOGISTIC REGRESSION| (e) (e) (e) (e) (e) | |COCH-ARM / FISHERS | (e) (e) (e) (e) (e) | |ORDER RESTRICTED | (e) (e) (e) (e) (e) | |=================================================================================================================================| Date: 04/14/04 EXPERIMENT: 99035 TEST: 01 Page 28 Statistical Analysis of Non-neoplastic Lesions in Mice(P16(INK4A)/(+/-) (C57BL/6)) - TRANSGENIC MODEL EVALUATION II ( GLY Terminal Sacrifice at 40 weeks |=================================================================================================================================| | | | | | Males | |Dose | 0 MG/KG 25 MG/KG 50 MG/KG 100 200 | | | MG/KG MG/KG | |=================================================================================================================================| | | |Spleen | | Hematopoietic Cell Proliferation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 4/15 (27%) 7/15 (47%) 7/15 (47%) 5/15 (33%) 5/15 (33%) | |POLY-3 RATE (b) | 4/15.00 7/15.00 7/15.00 5/14.37 5/12.79 | |POLY-3 PERCENT (g) | 26.7% 46.7% 46.7% 34.8% 39.1% | |TERMINAL (d) | 2/13 (15%) 6/14 (43%) 5/13 (39%) 5/14 (36%) 2/7 (29%) | |FIRST INCIDENCE | 196 253 146 280 (T) 208 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.283 P=0.295 P=0.256 P=0.538 P=0.283 | |POLY 3 | P=0.504 P=0.227 P=0.227 P=0.470 P=0.388 | |POLY 1.5 | P=0.557N P=0.227 P=0.227 P=0.482 P=0.434 | |POLY 6 | P=0.429 P=0.227 P=0.227 P=0.459 P=0.335 | |LOGISTIC REGRESSION| P=0.291N (e) (e) P=0.464 P=0.625N | |COCH-ARM / FISHERS | P=0.466N P=0.225 P=0.225 P=0.500 P=0.500 | |ORDER RESTRICTED | P=0.372 (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 MG/KG 25 MG/KG 50 MG/KG 100 200 | | | MG/KG MG/KG | |=================================================================================================================================| | | |Spleen | | Hematopoietic Cell Proliferation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 9/15 (60%) 5/15 (33%) 10/15 (67%) 10/15 (67%) 10/15 (67%) | |POLY-3 RATE (b) | 9/15.00 5/15.00 10/15.00 10/14.62 10/14.41 | |POLY-3 PERCENT (g) | 60.0% 33.3% 66.7% 68.4% 69.4% | |TERMINAL (d) | 7/13 (54%) 4/14 (29%) 7/12 (58%) 10/14 (71%) 5/9 (56%) | |FIRST INCIDENCE | 83 239 232 281 (T) 133 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.046 * P=0.135N P=0.434 P=0.585 P=0.235 | |POLY 3 | P=0.134 P=0.136N P=0.500 P=0.463 P=0.442 | |POLY 1.5 | P=0.152 P=0.136N P=0.500 P=0.480 P=0.465 | |POLY 6 | P=0.117 P=0.136N P=0.500 P=0.440 P=0.418 | |LOGISTIC REGRESSION| P=0.254 (e) (e) P=0.468 P=0.574 | |COCH-ARM / FISHERS | P=0.181 P=0.136N P=0.500 P=0.500 P=0.500 | |ORDER RESTRICTED | P=0.169 (e) (e) (e) (e) | |=================================================================================================================================| Date: 04/14/04 EXPERIMENT: 99035 TEST: 01 Page 29 Statistical Analysis of Non-neoplastic Lesions in Mice(P16(INK4A)/(+/-) (C57BL/6)) - TRANSGENIC MODEL EVALUATION II ( GLY Terminal Sacrifice at 40 weeks |=================================================================================================================================| | | | | | Males | |Dose | 0 MG/KG 25 MG/KG 50 MG/KG 100 200 | | | MG/KG MG/KG | |=================================================================================================================================| | | |Stomach, Forestomach | | Ulcer | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/15 (0%) 1/15 (7%) 0/15 (0%) 0/15 (0%) 3/15 (20%) | |POLY-3 RATE (b) | 0/13.95 1/15.00 0/13.80 0/14.37 3/12.19 | |POLY-3 PERCENT (g) | 0.0% 6.7% 0.0% 0.0% 24.6% | |TERMINAL (d) | 0/13 (0%) 0/14 (0%) 0/13 (0%) 0/14 (0%) 1/7 (14%) | |FIRST INCIDENCE | --- 253 --- --- 181 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.009 ** P=0.529 (e) (e) P=0.066 | |POLY 3 | P=0.017 * P=0.514 (e) (e) P=0.080 | |POLY 1.5 | P=0.018 * P=0.509 (e) (e) P=0.091 | |POLY 6 | P=0.017 * P=0.521 (e) (e) P=0.067 | |LOGISTIC REGRESSION| P=0.054 P=0.372 (e) (e) P=0.155 | |COCH-ARM / FISHERS | P=0.023 * P=0.500 (e) (e) P=0.112 | |ORDER RESTRICTED | P=0.005 ** (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 MG/KG 25 MG/KG 50 MG/KG 100 200 | | | MG/KG MG/KG | |=================================================================================================================================| | | |Stomach, Forestomach | | Ulcer | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/15 (0%) 0/15 (0%) 0/15 (0%) 0/15 (0%) 0/15 (0%) | |POLY-3 RATE (b) | 0/13.88 0/14.62 0/14.15 0/14.62 0/12.41 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 0/13 (0%) 0/14 (0%) 0/12 (0%) 0/14 (0%) 0/9 (0%) | |FIRST INCIDENCE | --- --- --- --- --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | (e) (e) (e) (e) (e) | |POLY 3 | (e) (e) (e) (e) (e) | |POLY 1.5 | (e) (e) (e) (e) (e) | |POLY 6 | (e) (e) (e) (e) (e) | |LOGISTIC REGRESSION| (e) (e) (e) (e) (e) | |COCH-ARM / FISHERS | (e) (e) (e) (e) (e) | |ORDER RESTRICTED | (e) (e) (e) (e) (e) | |=================================================================================================================================| Date: 04/14/04 EXPERIMENT: 99035 TEST: 01 Page 30 Statistical Analysis of Non-neoplastic Lesions in Mice(P16(INK4A)/(+/-) (C57BL/6)) - TRANSGENIC MODEL EVALUATION II ( GLY Terminal Sacrifice at 40 weeks |=================================================================================================================================| | | | | | Males | |Dose | 0 MG/KG 25 MG/KG 50 MG/KG 100 200 | | | MG/KG MG/KG | |=================================================================================================================================| | | |Stomach, Forestomach: Epithelium | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/15 (0%) 1/15 (7%) 1/15 (7%) 0/15 (0%) 6/15 (40%) | |POLY-3 RATE (b) | 0/13.95 1/15.00 1/14.14 0/14.37 6/13.56 | |POLY-3 PERCENT (g) | 0.0% 6.7% 7.1% 0.0% 44.3% | |TERMINAL (d) | 0/13 (0%) 0/14 (0%) 0/13 (0%) 0/14 (0%) 1/7 (14%) | |FIRST INCIDENCE | --- 253 244 --- 181 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P<0.001 ** P=0.529 P=0.515 (e) P=0.009 ** | |POLY 3 | P<0.001 ** P=0.514 P=0.503 (e) P=0.004 ** | |POLY 1.5 | P<0.001 ** P=0.509 P=0.500 (e) P=0.004 ** | |POLY 6 | P<0.001 ** P=0.521 P=0.508 (e) P=0.003 ** | |LOGISTIC REGRESSION| P=0.005 ** P=0.372 P=0.538 (e) P=0.031 * | |COCH-ARM / FISHERS | P<0.001 ** P=0.500 P=0.500 (e) P=0.008 ** | |ORDER RESTRICTED | P<0.001 ** (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 MG/KG 25 MG/KG 50 MG/KG 100 200 | | | MG/KG MG/KG | |=================================================================================================================================| | | |Stomach, Forestomach: Epithelium | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/15 (0%) 0/15 (0%) 0/15 (0%) 1/15 (7%) 4/15 (27%) | |POLY-3 RATE (b) | 0/13.88 0/14.62 0/14.15 1/14.62 4/13.12 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 6.8% 30.5% | |TERMINAL (d) | 0/13 (0%) 0/14 (0%) 0/12 (0%) 1/14 (7%) 3/9 (33%) | |FIRST INCIDENCE | --- --- --- 281 (T) 186 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P<0.001 ** (e) (e) P=0.515 P=0.031 * | |POLY 3 | P<0.001 ** (e) (e) P=0.510 P=0.037 * | |POLY 1.5 | P<0.001 ** (e) (e) P=0.510 P=0.041 * | |POLY 6 | P<0.001 ** (e) (e) P=0.509 P=0.033 * | |LOGISTIC REGRESSION| P<0.001 ** (e) (e) P=0.515 P=0.055 | |COCH-ARM / FISHERS | P<0.001 ** (e) (e) P=0.500 P=0.050 | |ORDER RESTRICTED | P<0.001 ** (e) (e) (e) (e) | |=================================================================================================================================| Date: 04/14/04 EXPERIMENT: 99035 TEST: 01 Page 31 Statistical Analysis of Non-neoplastic Lesions in Mice(P16(INK4A)/(+/-) (C57BL/6)) - TRANSGENIC MODEL EVALUATION II ( GLY Terminal Sacrifice at 40 weeks |=================================================================================================================================| | | | | | Males | |Dose | 0 MG/KG 25 MG/KG 50 MG/KG 100 200 | | | MG/KG MG/KG | |=================================================================================================================================| | | |Stomach, Glandular | | Mineralization | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 10/15 (67%) 0/15 (0%) 0/15 (0%) 5/15 (33%) 1/15 (7%) | |POLY-3 RATE (b) | 10/13.95 0/14.74 0/13.80 5/14.37 1/11.42 | |POLY-3 PERCENT (g) | 71.7% 0.0% 0.0% 34.8% 8.8% | |TERMINAL (d) | 10/13 (77%) 0/14 (0%) 0/13 (0%) 5/14 (36%) 1/7 (14%) | |FIRST INCIDENCE | 280 (T) --- --- 280 (T) 280 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.120N P<0.001N** P<0.001N** P=0.042N* P=0.015N* | |POLY 3 | P=0.028N* P<0.001N** P<0.001N** P=0.047N* P<0.001N** | |POLY 1.5 | P=0.020N* P<0.001N** P<0.001N** P=0.054N P<0.001N** | |POLY 6 | P=0.040N* P<0.001N** P<0.001N** P=0.040N* P<0.001N** | |LOGISTIC REGRESSION| P=0.120N (e) (e) P=0.042N* P=0.015N* | |COCH-ARM / FISHERS | P=0.036N* P<0.001N** P<0.001N** P=0.072N P<0.001N** | |ORDER RESTRICTED | P<0.001N** (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 MG/KG 25 MG/KG 50 MG/KG 100 200 | | | MG/KG MG/KG | |=================================================================================================================================| | | |Stomach, Glandular | | Mineralization | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 4/15 (27%) 0/15 (0%) 0/15 (0%) 0/15 (0%) 2/15 (13%) | |POLY-3 RATE (b) | 4/13.88 0/14.62 0/14.15 0/14.62 2/12.41 | |POLY-3 PERCENT (g) | 28.8% 0.0% 0.0% 0.0% 16.1% | |TERMINAL (d) | 4/13 (31%) 0/14 (0%) 0/12 (0%) 0/14 (0%) 2/9 (22%) | |FIRST INCIDENCE | 281 (T) --- --- --- 281 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.625N P=0.047N* P=0.064N P=0.047N* P=0.517N | |POLY 3 | P=0.496N P=0.038N* P=0.042N* P=0.038N* P=0.381N | |POLY 1.5 | P=0.505N P=0.039N* P=0.041N* P=0.039N* P=0.354N | |POLY 6 | P=0.483N P=0.039N* P=0.044N* P=0.039N* P=0.411N | |LOGISTIC REGRESSION| P=0.625N (e) (e) (e) P=0.517N | |COCH-ARM / FISHERS | P=0.500N P=0.050N P=0.050N P=0.050N P=0.326N | |ORDER RESTRICTED | P=0.013N* (e) (e) (e) (e) | |=================================================================================================================================| Date: 04/14/04 EXPERIMENT: 99035 TEST: 01 Page 32 Statistical Analysis of Non-neoplastic Lesions in Mice(P16(INK4A)/(+/-) (C57BL/6)) - TRANSGENIC MODEL EVALUATION II ( GLY Terminal Sacrifice at 40 weeks |=================================================================================================================================| | | | | | Males | |Dose | 0 MG/KG 25 MG/KG 50 MG/KG 100 200 | | | MG/KG MG/KG | |=================================================================================================================================| | | |Stomach, Glandular: Muscularis | | Mineralization | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/15 (0%) 0/15 (0%) 0/15 (0%) 1/15 (7%) 0/15 (0%) | |POLY-3 RATE (b) | 0/13.95 0/14.74 0/13.80 1/14.37 0/11.42 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 7.0% 0.0% | |TERMINAL (d) | 0/13 (0%) 0/14 (0%) 0/13 (0%) 1/14 (7%) 0/7 (0%) | |FIRST INCIDENCE | --- --- --- 280 (T) --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.580 (e) (e) P=0.515 (e) | |POLY 3 | P=0.512 (e) (e) P=0.506 (e) | |POLY 1.5 | P=0.570 (e) (e) P=0.503 (e) | |POLY 6 | P=0.431 (e) (e) P=0.509 (e) | |LOGISTIC REGRESSION| (e) (e) (e) P=0.515 (e) | |COCH-ARM / FISHERS | P=0.639 (e) (e) P=0.500 (e) | |ORDER RESTRICTED | P=0.387 (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 MG/KG 25 MG/KG 50 MG/KG 100 200 | | | MG/KG MG/KG | |=================================================================================================================================| | | |Stomach, Glandular: Muscularis | | Mineralization | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/15 (0%) 0/15 (0%) 0/15 (0%) 0/15 (0%) 2/15 (13%) | |POLY-3 RATE (b) | 0/13.88 0/14.62 0/14.15 0/14.62 2/12.41 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 0.0% 16.1% | |TERMINAL (d) | 0/13 (0%) 0/14 (0%) 0/12 (0%) 0/14 (0%) 2/9 (22%) | |FIRST INCIDENCE | --- --- --- --- 281 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.009 ** (e) (e) (e) P=0.157 | |POLY 3 | P=0.017 * (e) (e) (e) P=0.205 | |POLY 1.5 | P=0.017 * (e) (e) (e) P=0.217 | |POLY 6 | P=0.016 * (e) (e) (e) P=0.193 | |LOGISTIC REGRESSION| (e) (e) (e) (e) P=0.157 | |COCH-ARM / FISHERS | P=0.021 * (e) (e) (e) P=0.241 | |ORDER RESTRICTED | P=0.010 * (e) (e) (e) (e) | |=================================================================================================================================| Date: 04/14/04 EXPERIMENT: 99035 TEST: 01 Page 33 Statistical Analysis of Non-neoplastic Lesions in Mice(P16(INK4A)/(+/-) (C57BL/6)) - TRANSGENIC MODEL EVALUATION II ( GLY Terminal Sacrifice at 40 weeks |=================================================================================================================================| | | | | | Males | |Dose | 0 MG/KG 25 MG/KG 50 MG/KG 100 200 | | | MG/KG MG/KG | |=================================================================================================================================| | | |Thymus | | Atrophy | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 2/15 (13%) 0/15 (0%) 1/15 (7%) 0/15 (0%) 4/15 (27%) | |POLY-3 RATE (b) | 2/15.00 0/14.74 1/14.66 0/14.37 4/12.77 | |POLY-3 PERCENT (g) | 13.3% 0.0% 6.8% 0.0% 31.3% | |TERMINAL (d) | 0/13 (0%) 0/14 (0%) 0/13 (0%) 0/14 (0%) 0/7 (0%) | |FIRST INCIDENCE | 196 --- 146 --- 210 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.039 * P=0.232N P=0.508N P=0.240N P=0.231 | |POLY 3 | P=0.048 * P=0.236N P=0.508N P=0.241N P=0.249 | |POLY 1.5 | P=0.051 P=0.234N P=0.504N P=0.238N P=0.280 | |POLY 6 | P=0.046 * P=0.239N P=0.514N P=0.245N P=0.217 | |LOGISTIC REGRESSION| P=0.367 (e) (e) P=0.207N P=0.662 | |COCH-ARM / FISHERS | P=0.061 P=0.241N P=0.500N P=0.241N P=0.326 | |ORDER RESTRICTED | P=0.013 * (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 MG/KG 25 MG/KG 50 MG/KG 100 200 | | | MG/KG MG/KG | |=================================================================================================================================| | | |Thymus | | Atrophy | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/15 (0%) 2/15 (13%) 0/15 (0%) 1/15 (7%) 3/15 (20%) | |POLY-3 RATE (b) | 0/13.88 2/15.00 0/14.15 1/14.62 3/14.05 | |POLY-3 PERCENT (g) | 0.0% 13.3% 0.0% 6.8% 21.4% | |TERMINAL (d) | 0/13 (0%) 1/14 (7%) 0/12 (0%) 1/14 (7%) 0/9 (0%) | |FIRST INCIDENCE | --- 239 --- 281 (T) 186 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.047 * P=0.256 (e) P=0.515 P=0.111 | |POLY 3 | P=0.066 P=0.250 (e) P=0.510 P=0.107 | |POLY 1.5 | P=0.066 P=0.246 (e) P=0.510 P=0.108 | |POLY 6 | P=0.067 P=0.252 (e) P=0.509 P=0.107 | |LOGISTIC REGRESSION| P=0.105 P=0.197 (e) P=0.515 P=0.108 | |COCH-ARM / FISHERS | P=0.066 P=0.241 (e) P=0.500 P=0.112 | |ORDER RESTRICTED | P=0.028 * (e) (e) (e) (e) | |=================================================================================================================================| Date: 04/14/04 EXPERIMENT: 99035 TEST: 01 Page 34 Statistical Analysis of Non-neoplastic Lesions in Mice(P16(INK4A)/(+/-) (C57BL/6)) - TRANSGENIC MODEL EVALUATION II ( GLY Terminal Sacrifice at 40 weeks |=================================================================================================================================| | | | | | Males | |Dose | 0 MG/KG 25 MG/KG 50 MG/KG 100 200 | | | MG/KG MG/KG | |=================================================================================================================================| | | |Uterus: Endometrium | | Hyperplasia Cystic | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | | |POLY-3 RATE (b) | | |POLY-3 PERCENT (g) | | |TERMINAL (d) | | |FIRST INCIDENCE | | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | | |POLY 3 | | |POLY 1.5 | | |POLY 6 | | |LOGISTIC REGRESSION| | |COCH-ARM / FISHERS | | |ORDER RESTRICTED | | |=================================================================================================================================| | | | | | Females | |Dose | 0 MG/KG 25 MG/KG 50 MG/KG 100 200 | | | MG/KG MG/KG | |=================================================================================================================================| | | |Uterus: Endometrium | | Hyperplasia Cystic | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 13/15 (87%) 14/15 (93%) 10/15 (67%) 14/15 (93%) 9/15 (60%) | |POLY-3 RATE (b) | 13/13.88 14/14.62 10/14.15 14/15.00 9/12.44 | |POLY-3 PERCENT (g) | 93.6% 95.8% 70.7% 93.3% 72.3% | |TERMINAL (d) | 13/13 (100%) 14/14 (100%) 10/12 (83%) 13/14 (93%) 8/9 (89%) | |FIRST INCIDENCE | 281 (T) 281 (T) 281 (T) 239 278 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.561 P=1.000 P=0.217N P=0.760 P=0.740N | |POLY 3 | P=0.109N P=0.741 P=0.121N P=0.765N P=0.146N | |POLY 1.5 | P=0.072N P=0.702 P=0.121N P=0.731 P=0.102N | |POLY 6 | P=0.155N P=0.767 P=0.138N P=0.742N P=0.221N | |LOGISTIC REGRESSION| P=0.259N P=1.000 P=0.217N P=0.716 (e) | |COCH-ARM / FISHERS | P=0.051N P=0.500 P=0.195N P=0.500 P=0.107N | |ORDER RESTRICTED | P=0.060N (e) (e) (e) (e) | |=================================================================================================================================| (a) Number of tumor-bearing animals / number of animals examined at site. (b) Number of tumor-bearing animals / Poly-3 number (d) Observed incidence at terminal kill. (f) Beneath the control incidence are the P-values associated with the trend test. Beneath the dosed group incidence are the P-values corresponding to pairwise comparisons between the controls and that dosed group. The life table analysis regards tumors in animals dying prior to terminal kill as being (directly or indirectly) the cause of death. Logistic regression is an alternative method for analyzing the incidence of non-fatal tumors. The Cochran-Armitage and Fishers exact tests compare directly the overall incidence rates For all tests a negative trend is indicated by N (e) Value of Statistic cannot be computed. (g) Poly-3 adjusted lifetime tumor incidence. (I) Interim sacrifice (T) Terminal sacrifice # Tumor rates based on number of animals necropsied. * To the right of any statistical result, indicates significance at (P<=0.05). ** To the right of any statistical result, indicates significance at (P<=0.01).