TDMS Study 99034-01 Pathology Tables
NTP STATISTICAL ANALYSIS OF NON-NEOPLASTIC LESIONS REPORT: PEIRPT10 LAB: Battelle Columbus TRANSGENIC MODEL EVALUATION II (BENZENE) DATE: 11/05/03 EXPERIMENT: 99034 TEST: 01 TIME: 14:55:50 TEST TYPE: SUBCHRON 26-WEEK CAGES FROM 0000 TO LAST CAGE PAGE: 1 CONT: N01-ES-65406 ROUTE: GAVAGE NTP C#: C99034 PATHOLOGIST: MISSING CAS: 71-43-2 ------------------------------------------------------------------------------------------------------------------------------------ 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 (BENZENE) DATE: 11/05/03 EXPERIMENT: 99034 TEST: 01 TIME: 14:55:50 TEST TYPE: SUBCHRON 26-WEEK CAGES FROM 0000 TO LAST CAGE CONT: N01-ES-65406 ROUTE: GAVAGE NTP C#: C99034 PATHOLOGIST: MISSING CAS: 71-43-2 SUMMARY OF STATISTICALLY SIGNIFICANT (P<=.05) RESULTS IN THE ANALYSIS OF TRANSGENIC MODEL EVALUATION II (BEN =============================================================== Male Mice ------------ Organ Morphology ----- ---------- Bone Marrow Atrophy Pigmentation Hemosiderin Kidney Nephropathy Lung Inflammation Chronic Lymph Node, Mandibular Atrophy Lymph Node, Mesenteric Atrophy Lymph Node: Mediastinal Atrophy Skin Pigmentation Spleen Hematopoietic Cell Proliferation Spleen: Lymphoid Follicle Atrophy Stomach, Forestomach Hyperplasia Thymus Atrophy =============================================================== Female Mice ------------ Organ Morphology ----- ---------- Liver Inflammation Chronic Lung: Alveolar Epithelium Hyperplasia Focal Lymph Node, Mesenteric Atrophy Lymph Node: Mediastinal Atrophy Mammary Gland Hyperplasia Skin Pigmentation Uterus: Endometrium Hyperplasia Cystic =============================================================== Date: 11/05/03 EXPERIMENT: 99034 TEST: 01 Page 1 Statistical Analysis of Non-neoplastic Lesions in Mice(P16(INK4A)/(+/-) (C57BL/6)) - TRANSGENIC MODEL EVALUATION II (BEN Terminal Sacrifice at 27 weeks |=================================================================================================================================| | | | | | Males | |Dose | 0 MG/KG 25 MG/KG 50 MG/KG 100 200 | | | MG/KG MG/KG | |=================================================================================================================================| | | |Bone Marrow | | Atrophy | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/15 (0%) 0/15 (0%) 0/15 (0%) 10/15 (67%) 12/15 (80%) | |POLY-3 RATE (b) | 0/15.00 0/15.00 0/15.00 10/15.00 12/14.00 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 66.7% 85.7% | |TERMINAL (d) | 0/15 (0%) 0/15 (0%) 0/15 (0%) 10/15 (67%) 12/14 (86%) | |FIRST INCIDENCE | --- --- --- 188 (T) 188 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P<0.001 ** (e) (e) P<0.001 ** P<0.001 ** | |POLY 3 | P<0.001 ** (e) (e) P<0.001 ** P<0.001 ** | |POLY 1.5 | P<0.001 ** (e) (e) P<0.001 ** P<0.001 ** | |POLY 6 | P<0.001 ** (e) (e) P<0.001 ** P<0.001 ** | |LOGISTIC REGRESSION| P<0.001 ** (e) (e) P<0.001 ** P<0.001 ** | |COCH-ARM / FISHERS | P<0.001 ** (e) (e) P<0.001 ** P<0.001 ** | |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 | |=================================================================================================================================| | | |Bone Marrow | | Atrophy | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/15 (0%) 0/15 (0%) 0/15 (0%) 0/15 (0%) 0/15 (0%) | |POLY-3 RATE (b) | 0/15.00 0/15.00 0/15.00 0/15.00 0/15.00 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 0/15 (0%) 0/15 (0%) 0/15 (0%) 0/15 (0%) 0/15 (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: 11/05/03 EXPERIMENT: 99034 TEST: 01 Page 2 Statistical Analysis of Non-neoplastic Lesions in Mice(P16(INK4A)/(+/-) (C57BL/6)) - TRANSGENIC MODEL EVALUATION II ( BEN Terminal Sacrifice at 27 weeks |=================================================================================================================================| | | | | | Males | |Dose | 0 MG/KG 25 MG/KG 50 MG/KG 100 200 | | | MG/KG MG/KG | |=================================================================================================================================| | | |Bone Marrow | | Pigmentation Hemosiderin | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 1/15 (7%) 13/15 (87%) 13/15 (87%) 15/15 (100%) 14/15 (93%) | |POLY-3 RATE (b) | 1/15.00 13/15.00 13/15.00 15/15.00 14/14.00 | |POLY-3 PERCENT (g) | 6.7% 86.7% 86.7% 100.0% 100.0% | |TERMINAL (d) | 1/15 (7%) 13/15 (87%) 13/15 (87%) 15/15 (100%) 14/14 (100%) | |FIRST INCIDENCE | 188 (T) 188 (T) 188 (T) 188 (T) 188 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** | |POLY 3 | P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** | |POLY 1.5 | P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** | |POLY 6 | P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** | |LOGISTIC REGRESSION| P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** | |COCH-ARM / FISHERS | P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** | |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 | |=================================================================================================================================| | | |Bone Marrow | | Pigmentation Hemosiderin | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/15 (0%) 0/15 (0%) 0/15 (0%) 0/15 (0%) 0/15 (0%) | |POLY-3 RATE (b) | 0/15.00 0/15.00 0/15.00 0/15.00 0/15.00 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 0/15 (0%) 0/15 (0%) 0/15 (0%) 0/15 (0%) 0/15 (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: 11/05/03 EXPERIMENT: 99034 TEST: 01 Page 3 Statistical Analysis of Non-neoplastic Lesions in Mice(P16(INK4A)/(+/-) (C57BL/6)) - TRANSGENIC MODEL EVALUATION II ( BEN Terminal Sacrifice at 27 weeks |=================================================================================================================================| | | | | | Males | |Dose | 0 MG/KG 25 MG/KG 50 MG/KG 100 200 | | | MG/KG MG/KG | |=================================================================================================================================| | | |Intestine Small, Duodenum | | Inflammation Chronic | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/15 (0%) 0/15 (0%) 0/15 (0%) 0/15 (0%) 0/15 (0%) | |POLY-3 RATE (b) | 0/15.00 0/15.00 0/15.00 0/15.00 0/14.00 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 0/15 (0%) 0/15 (0%) 0/15 (0%) 0/15 (0%) 0/14 (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 | |=================================================================================================================================| | | |Intestine Small, Duodenum | | Inflammation Chronic | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/15 (0%) 0/15 (0%) 0/15 (0%) 2/15 (13%) 0/15 (0%) | |POLY-3 RATE (b) | 0/15.00 0/15.00 0/15.00 2/15.00 0/15.00 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 13.3% 0.0% | |TERMINAL (d) | 0/15 (0%) 0/15 (0%) 0/15 (0%) 2/15 (13%) 0/15 (0%) | |FIRST INCIDENCE | --- --- --- 189 (T) --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.500 (e) (e) P=0.236 (e) | |POLY 3 | P=0.500 (e) (e) P=0.232 (e) | |POLY 1.5 | P=0.500 (e) (e) P=0.232 (e) | |POLY 6 | P=0.500 (e) (e) P=0.232 (e) | |LOGISTIC REGRESSION| (e) (e) (e) P=0.236 (e) | |COCH-ARM / FISHERS | P=0.500 (e) (e) P=0.241 (e) | |ORDER RESTRICTED | P=0.205 (e) (e) (e) (e) | |=================================================================================================================================| Date: 11/05/03 EXPERIMENT: 99034 TEST: 01 Page 4 Statistical Analysis of Non-neoplastic Lesions in Mice(P16(INK4A)/(+/-) (C57BL/6)) - TRANSGENIC MODEL EVALUATION II ( BEN Terminal Sacrifice at 27 weeks |=================================================================================================================================| | | | | | Males | |Dose | 0 MG/KG 25 MG/KG 50 MG/KG 100 200 | | | MG/KG MG/KG | |=================================================================================================================================| | | |Kidney | | Casts Protein | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 1/15 (7%) 0/15 (0%) 2/15 (13%) 1/15 (7%) 2/15 (13%) | |POLY-3 RATE (b) | 1/15.00 0/15.00 2/15.00 1/15.00 2/14.00 | |POLY-3 PERCENT (g) | 6.7% 0.0% 13.3% 6.7% 14.3% | |TERMINAL (d) | 1/15 (7%) 0/15 (0%) 2/15 (13%) 1/15 (7%) 2/14 (14%) | |FIRST INCIDENCE | 188 (T) --- 188 (T) 188 (T) 188 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.252 P=0.500N P=0.500 P=0.764 P=0.475 | |POLY 3 | P=0.254 P=0.500N P=0.500 P=0.760 P=0.476 | |POLY 1.5 | P=0.254 P=0.500N P=0.500 P=0.760 P=0.476 | |POLY 6 | P=0.254 P=0.500N P=0.500 P=0.760 P=0.476 | |LOGISTIC REGRESSION| P=0.252 (e) P=0.500 P=0.764 P=0.475 | |COCH-ARM / FISHERS | P=0.274 P=0.500N P=0.500 P=0.759N P=0.500 | |ORDER RESTRICTED | P=0.250 (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 MG/KG 25 MG/KG 50 MG/KG 100 200 | | | MG/KG MG/KG | |=================================================================================================================================| | | |Kidney | | Casts Protein | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 5/15 (33%) 4/15 (27%) 5/15 (33%) 8/15 (53%) 7/15 (47%) | |POLY-3 RATE (b) | 5/15.00 4/15.00 5/15.00 8/15.00 7/15.00 | |POLY-3 PERCENT (g) | 33.3% 26.7% 33.3% 53.3% 46.7% | |TERMINAL (d) | 5/15 (33%) 4/15 (27%) 5/15 (33%) 8/15 (53%) 7/15 (47%) | |FIRST INCIDENCE | 189 (T) 189 (T) 189 (T) 189 (T) 189 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.140 P=0.500N P=0.648 P=0.234 P=0.357 | |POLY 3 | P=0.141 P=0.500N P=0.646 P=0.234 P=0.358 | |POLY 1.5 | P=0.141 P=0.500N P=0.646 P=0.234 P=0.358 | |POLY 6 | P=0.141 P=0.500N P=0.646 P=0.234 P=0.358 | |LOGISTIC REGRESSION| P=0.140 P=0.500N P=0.648 P=0.234 P=0.357 | |COCH-ARM / FISHERS | P=0.138 P=0.500N P=0.650N P=0.231 P=0.355 | |ORDER RESTRICTED | P=0.225 (e) (e) (e) (e) | |=================================================================================================================================| Date: 11/05/03 EXPERIMENT: 99034 TEST: 01 Page 5 Statistical Analysis of Non-neoplastic Lesions in Mice(P16(INK4A)/(+/-) (C57BL/6)) - TRANSGENIC MODEL EVALUATION II ( BEN Terminal Sacrifice at 27 weeks |=================================================================================================================================| | | | | | Males | |Dose | 0 MG/KG 25 MG/KG 50 MG/KG 100 200 | | | MG/KG MG/KG | |=================================================================================================================================| | | |Kidney | | Nephropathy | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 1/15 (7%) 1/15 (7%) 0/15 (0%) 2/15 (13%) 4/15 (27%) | |POLY-3 RATE (b) | 1/15.00 1/15.00 0/15.00 2/15.00 4/14.00 | |POLY-3 PERCENT (g) | 6.7% 6.7% 0.0% 13.3% 28.6% | |TERMINAL (d) | 1/15 (7%) 1/15 (7%) 0/15 (0%) 2/15 (13%) 4/14 (29%) | |FIRST INCIDENCE | 188 (T) 188 (T) --- 188 (T) 188 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.019 * P=0.764 P=0.500N P=0.500 P=0.147 | |POLY 3 | P=0.019 * P=0.760 P=0.500N P=0.500 P=0.141 | |POLY 1.5 | P=0.019 * P=0.760 P=0.500N P=0.500 P=0.141 | |POLY 6 | P=0.019 * P=0.760 P=0.500N P=0.500 P=0.141 | |LOGISTIC REGRESSION| P=0.019 * P=0.764 (e) P=0.500 P=0.143 | |COCH-ARM / FISHERS | P=0.024 * P=0.759N P=0.500N P=0.500 P=0.165 | |ORDER RESTRICTED | P=0.024 * (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) | 3/15 (20%) 0/15 (0%) 1/15 (7%) 2/15 (13%) 1/15 (7%) | |POLY-3 RATE (b) | 3/15.00 0/15.00 1/15.00 2/15.00 1/15.00 | |POLY-3 PERCENT (g) | 20.0% 0.0% 6.7% 13.3% 6.7% | |TERMINAL (d) | 3/15 (20%) 0/15 (0%) 1/15 (7%) 2/15 (13%) 1/15 (7%) | |FIRST INCIDENCE | 189 (T) --- 189 (T) 189 (T) 189 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.445N P=0.116N P=0.299N P=0.500N P=0.299N | |POLY 3 | P=0.445N P=0.106N P=0.298N P=0.500N P=0.298N | |POLY 1.5 | P=0.445N P=0.106N P=0.298N P=0.500N P=0.298N | |POLY 6 | P=0.445N P=0.106N P=0.298N P=0.500N P=0.298N | |LOGISTIC REGRESSION| P=0.445N (e) P=0.299N P=0.500N P=0.299N | |COCH-ARM / FISHERS | P=0.444N P=0.112N P=0.299N P=0.500N P=0.299N | |ORDER RESTRICTED | P=0.175N (e) (e) (e) (e) | |=================================================================================================================================| Date: 11/05/03 EXPERIMENT: 99034 TEST: 01 Page 6 Statistical Analysis of Non-neoplastic Lesions in Mice(P16(INK4A)/(+/-) (C57BL/6)) - TRANSGENIC MODEL EVALUATION II ( BEN Terminal Sacrifice at 27 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) | 3/15 (20%) 6/15 (40%) 1/15 (7%) 3/15 (20%) 1/15 (7%) | |POLY-3 RATE (b) | 3/15.00 6/15.00 1/15.00 3/15.00 1/14.00 | |POLY-3 PERCENT (g) | 20.0% 40.0% 6.7% 20.0% 7.1% | |TERMINAL (d) | 3/15 (20%) 6/15 (40%) 1/15 (7%) 3/15 (20%) 1/14 (7%) | |FIRST INCIDENCE | 188 (T) 188 (T) 188 (T) 188 (T) 188 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.121N P=0.217 P=0.299N P=0.673 P=0.324N | |POLY 3 | P=0.118N P=0.215 P=0.298N P=0.670 P=0.324N | |POLY 1.5 | P=0.118N P=0.215 P=0.298N P=0.670 P=0.324N | |POLY 6 | P=0.118N P=0.215 P=0.298N P=0.670 P=0.324N | |LOGISTIC REGRESSION| P=0.121N P=0.217 P=0.299N P=0.673 P=0.324N | |COCH-ARM / FISHERS | P=0.104N P=0.213 P=0.299N P=0.674N P=0.299N | |ORDER RESTRICTED | P=0.088N (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) | 10/15 (67%) 6/15 (40%) 6/15 (40%) 4/15 (27%) 11/15 (73%) | |POLY-3 RATE (b) | 10/15.00 6/15.00 6/15.00 4/15.00 11/15.00 | |POLY-3 PERCENT (g) | 66.7% 40.0% 40.0% 26.7% 73.3% | |TERMINAL (d) | 10/15 (67%) 6/15 (40%) 6/15 (40%) 4/15 (27%) 11/15 (73%) | |FIRST INCIDENCE | 189 (T) 189 (T) 189 (T) 189 (T) 189 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.233 P=0.140N P=0.140N P=0.036N* P=0.500 | |POLY 3 | P=0.224 P=0.136N P=0.136N P=0.027N* P=0.500 | |POLY 1.5 | P=0.224 P=0.136N P=0.136N P=0.027N* P=0.500 | |POLY 6 | P=0.224 P=0.136N P=0.136N P=0.027N* P=0.500 | |LOGISTIC REGRESSION| P=0.233 P=0.140N P=0.140N P=0.036N* P=0.500 | |COCH-ARM / FISHERS | P=0.231 P=0.136N P=0.136N P=0.033N* P=0.500 | |ORDER RESTRICTED | P=0.066 (e) (e) (e) (e) | |=================================================================================================================================| Date: 11/05/03 EXPERIMENT: 99034 TEST: 01 Page 7 Statistical Analysis of Non-neoplastic Lesions in Mice(P16(INK4A)/(+/-) (C57BL/6)) - TRANSGENIC MODEL EVALUATION II ( BEN Terminal Sacrifice at 27 weeks |=================================================================================================================================| | | | | | Males | |Dose | 0 MG/KG 25 MG/KG 50 MG/KG 100 200 | | | MG/KG MG/KG | |=================================================================================================================================| | | |Lung | | Inflammation Chronic | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 2/15 (13%) 0/15 (0%) 1/15 (7%) 3/15 (20%) 5/15 (33%) | |POLY-3 RATE (b) | 2/15.00 0/15.00 1/15.00 3/15.00 5/14.00 | |POLY-3 PERCENT (g) | 13.3% 0.0% 6.7% 20.0% 35.7% | |TERMINAL (d) | 2/15 (13%) 0/15 (0%) 1/15 (7%) 3/15 (20%) 5/14 (36%) | |FIRST INCIDENCE | 188 (T) --- 188 (T) 188 (T) 188 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.011 * P=0.236N P=0.500N P=0.500 P=0.169 | |POLY 3 | P=0.010 * P=0.232N P=0.500N P=0.500 P=0.166 | |POLY 1.5 | P=0.010 * P=0.232N P=0.500N P=0.500 P=0.166 | |POLY 6 | P=0.010 * P=0.232N P=0.500N P=0.500 P=0.166 | |LOGISTIC REGRESSION| P=0.011 * (e) P=0.500N P=0.500 P=0.169 | |COCH-ARM / FISHERS | P=0.014 * P=0.241N P=0.500N P=0.500 P=0.195 | |ORDER RESTRICTED | P=0.018 * (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 MG/KG 25 MG/KG 50 MG/KG 100 200 | | | MG/KG MG/KG | |=================================================================================================================================| | | |Lung | | Inflammation Chronic | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 2/15 (13%) 2/15 (13%) 0/15 (0%) 0/15 (0%) 2/15 (13%) | |POLY-3 RATE (b) | 2/15.00 2/15.00 0/15.00 0/15.00 2/15.00 | |POLY-3 PERCENT (g) | 13.3% 13.3% 0.0% 0.0% 13.3% | |TERMINAL (d) | 2/15 (13%) 2/15 (13%) 0/15 (0%) 0/15 (0%) 2/15 (13%) | |FIRST INCIDENCE | 189 (T) 189 (T) --- --- 189 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.618 P=0.701 P=0.236N P=0.236N P=0.701 | |POLY 3 | P=0.618 P=0.698 P=0.232N P=0.232N P=0.698 | |POLY 1.5 | P=0.618 P=0.698 P=0.232N P=0.232N P=0.698 | |POLY 6 | P=0.618 P=0.698 P=0.232N P=0.232N P=0.698 | |LOGISTIC REGRESSION| P=0.618 P=0.701 (e) (e) P=0.701 | |COCH-ARM / FISHERS | P=0.618 P=0.701N P=0.241N P=0.241N P=0.701N | |ORDER RESTRICTED | P=0.322N (e) (e) (e) (e) | |=================================================================================================================================| Date: 11/05/03 EXPERIMENT: 99034 TEST: 01 Page 8 Statistical Analysis of Non-neoplastic Lesions in Mice(P16(INK4A)/(+/-) (C57BL/6)) - TRANSGENIC MODEL EVALUATION II ( BEN Terminal Sacrifice at 27 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%) 0/15 (0%) 1/15 (7%) 0/15 (0%) 0/15 (0%) | |POLY-3 RATE (b) | 0/15.00 0/15.00 1/15.00 0/15.00 0/14.00 | |POLY-3 PERCENT (g) | 0.0% 0.0% 6.7% 0.0% 0.0% | |TERMINAL (d) | 0/15 (0%) 0/15 (0%) 1/15 (7%) 0/15 (0%) 0/14 (0%) | |FIRST INCIDENCE | --- --- 188 (T) --- --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.649N (e) P=0.500 (e) (e) | |POLY 3 | P=0.639N (e) P=0.500 (e) (e) | |POLY 1.5 | P=0.639N (e) P=0.500 (e) (e) | |POLY 6 | P=0.639N (e) P=0.500 (e) (e) | |LOGISTIC REGRESSION| (e) (e) P=0.500 (e) (e) | |COCH-ARM / FISHERS | P=0.639N (e) P=0.500 (e) (e) | |ORDER RESTRICTED | P=0.522 (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%) 0/15 (0%) 0/15 (0%) 0/15 (0%) 3/15 (20%) | |POLY-3 RATE (b) | 1/15.00 0/15.00 0/15.00 0/15.00 3/15.00 | |POLY-3 PERCENT (g) | 6.7% 0.0% 0.0% 0.0% 20.0% | |TERMINAL (d) | 1/15 (7%) 0/15 (0%) 0/15 (0%) 0/15 (0%) 3/15 (20%) | |FIRST INCIDENCE | 189 (T) --- --- --- 189 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.036 * P=0.500N P=0.500N P=0.500N P=0.299 | |POLY 3 | P=0.031 * P=0.500N P=0.500N P=0.500N P=0.298 | |POLY 1.5 | P=0.031 * P=0.500N P=0.500N P=0.500N P=0.298 | |POLY 6 | P=0.031 * P=0.500N P=0.500N P=0.500N P=0.298 | |LOGISTIC REGRESSION| P=0.036 * (e) (e) (e) P=0.299 | |COCH-ARM / FISHERS | P=0.035 * P=0.500N P=0.500N P=0.500N P=0.299 | |ORDER RESTRICTED | P=0.014 * (e) (e) (e) (e) | |=================================================================================================================================| Date: 11/05/03 EXPERIMENT: 99034 TEST: 01 Page 9 Statistical Analysis of Non-neoplastic Lesions in Mice(P16(INK4A)/(+/-) (C57BL/6)) - TRANSGENIC MODEL EVALUATION II ( BEN Terminal Sacrifice at 27 weeks |=================================================================================================================================| | | | | | Males | |Dose | 0 MG/KG 25 MG/KG 50 MG/KG 100 200 | | | MG/KG MG/KG | |=================================================================================================================================| | | |Lymph Node, Mandibular | | Atrophy | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/15 (0%) 0/15 (0%) 0/15 (0%) 6/14 (43%) 11/14 (79%) | |POLY-3 RATE (b) | 0/15.00 0/15.00 0/15.00 6/14.00 11/13.00 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 42.9% 84.6% | |TERMINAL (d) | 0/15 (0%) 0/15 (0%) 0/15 (0%) 6/14 (43%) 11/13 (85%) | |FIRST INCIDENCE | --- --- --- 188 (T) 188 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P<0.001 ** (e) (e) P=0.009 ** P<0.001 ** | |POLY 3 | P<0.001 ** (e) (e) P=0.003 ** P<0.001 ** | |POLY 1.5 | P<0.001 ** (e) (e) P=0.003 ** P<0.001 ** | |POLY 6 | P<0.001 ** (e) (e) P=0.003 ** P<0.001 ** | |LOGISTIC REGRESSION| P<0.001 ** (e) (e) P=0.009 ** P<0.001 ** | |COCH-ARM / FISHERS | P<0.001 ** (e) (e) P=0.006 ** P<0.001 ** | |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 | |=================================================================================================================================| | | |Lymph Node, Mandibular | | Atrophy | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/14 (0%) 1/15 (7%) 2/15 (13%) 4/15 (27%) 0/15 (0%) | |POLY-3 RATE (b) | 0/14.00 1/15.00 2/15.00 4/15.00 0/15.00 | |POLY-3 PERCENT (g) | 0.0% 6.7% 13.3% 26.7% 0.0% | |TERMINAL (d) | 0/14 (0%) 1/15 (7%) 2/15 (13%) 4/15 (27%) 0/15 (0%) | |FIRST INCIDENCE | --- 189 (T) 189 (T) 189 (T) --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.595N P=0.514 P=0.251 P=0.065 (e) | |POLY 3 | P=0.598N P=0.514 P=0.247 P=0.053 (e) | |POLY 1.5 | P=0.598N P=0.514 P=0.247 P=0.053 (e) | |POLY 6 | P=0.598N P=0.514 P=0.247 P=0.053 (e) | |LOGISTIC REGRESSION| (e) P=0.514 P=0.251 P=0.065 (e) | |COCH-ARM / FISHERS | P=0.595N P=0.517 P=0.259 P=0.057 (e) | |ORDER RESTRICTED | P=0.176 (e) (e) (e) (e) | |=================================================================================================================================| Date: 11/05/03 EXPERIMENT: 99034 TEST: 01 Page 10 Statistical Analysis of Non-neoplastic Lesions in Mice(P16(INK4A)/(+/-) (C57BL/6)) - TRANSGENIC MODEL EVALUATION II ( BEN Terminal Sacrifice at 27 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) | 2/15 (13%) 1/15 (7%) 1/15 (7%) 0/14 (0%) 0/14 (0%) | |POLY-3 RATE (b) | 2/15.00 1/15.00 1/15.00 0/14.00 0/13.00 | |POLY-3 PERCENT (g) | 13.3% 6.7% 6.7% 0.0% 0.0% | |TERMINAL (d) | 2/15 (13%) 1/15 (7%) 1/15 (7%) 0/14 (0%) 0/13 (0%) | |FIRST INCIDENCE | 188 (T) 188 (T) 188 (T) --- --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.118N P=0.500N P=0.500N P=0.251N P=0.268N | |POLY 3 | P=0.115N P=0.500N P=0.500N P=0.247N P=0.265N | |POLY 1.5 | P=0.115N P=0.500N P=0.500N P=0.247N P=0.265N | |POLY 6 | P=0.115N P=0.500N P=0.500N P=0.247N P=0.265N | |LOGISTIC REGRESSION| P=0.118N P=0.500N P=0.500N (e) (e) | |COCH-ARM / FISHERS | P=0.110N P=0.500N P=0.500N P=0.259N P=0.259N | |ORDER RESTRICTED | P=0.107N (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) | 1/14 (7%) 4/15 (27%) 2/15 (13%) 5/15 (33%) 3/15 (20%) | |POLY-3 RATE (b) | 1/14.00 4/15.00 2/15.00 5/15.00 3/15.00 | |POLY-3 PERCENT (g) | 7.1% 26.7% 13.3% 33.3% 20.0% | |TERMINAL (d) | 1/14 (7%) 4/15 (27%) 2/15 (13%) 5/15 (33%) 3/15 (20%) | |FIRST INCIDENCE | 189 (T) 189 (T) 189 (T) 189 (T) 189 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.328 P=0.189 P=0.525 P=0.104 P=0.324 | |POLY 3 | P=0.328 P=0.185 P=0.524 P=0.096 P=0.324 | |POLY 1.5 | P=0.328 P=0.185 P=0.524 P=0.096 P=0.324 | |POLY 6 | P=0.328 P=0.185 P=0.524 P=0.096 P=0.324 | |LOGISTIC REGRESSION| P=0.328 P=0.189 P=0.525 P=0.104 P=0.324 | |COCH-ARM / FISHERS | P=0.327 P=0.186 P=0.527 P=0.099 P=0.326 | |ORDER RESTRICTED | P=0.163 (e) (e) (e) (e) | |=================================================================================================================================| Date: 11/05/03 EXPERIMENT: 99034 TEST: 01 Page 11 Statistical Analysis of Non-neoplastic Lesions in Mice(P16(INK4A)/(+/-) (C57BL/6)) - TRANSGENIC MODEL EVALUATION II ( BEN Terminal Sacrifice at 27 weeks |=================================================================================================================================| | | | | | Males | |Dose | 0 MG/KG 25 MG/KG 50 MG/KG 100 200 | | | MG/KG MG/KG | |=================================================================================================================================| | | |Lymph Node, Mandibular | | Infiltration Cellular Polymorphonuclear | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/15 (0%) 0/15 (0%) 0/15 (0%) 1/14 (7%) 1/14 (7%) | |POLY-3 RATE (b) | 0/15.00 0/15.00 0/15.00 1/14.00 1/13.00 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 7.1% 7.7% | |TERMINAL (d) | 0/15 (0%) 0/15 (0%) 0/15 (0%) 1/14 (7%) 1/13 (8%) | |FIRST INCIDENCE | --- --- --- 188 (T) 188 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.133 (e) (e) P=0.486 P=0.471 | |POLY 3 | P=0.130 (e) (e) P=0.486 P=0.471 | |POLY 1.5 | P=0.130 (e) (e) P=0.486 P=0.472 | |POLY 6 | P=0.130 (e) (e) P=0.486 P=0.471 | |LOGISTIC REGRESSION| P=0.131 (e) (e) P=0.486 P=0.471 | |COCH-ARM / FISHERS | P=0.143 (e) (e) P=0.483 P=0.483 | |ORDER RESTRICTED | P=0.192 (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 MG/KG 25 MG/KG 50 MG/KG 100 200 | | | MG/KG MG/KG | |=================================================================================================================================| | | |Lymph Node, Mandibular | | Infiltration Cellular Polymorphonuclear | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 1/14 (7%) 0/15 (0%) 0/15 (0%) 0/15 (0%) 2/15 (13%) | |POLY-3 RATE (b) | 1/14.00 0/15.00 0/15.00 0/15.00 2/15.00 | |POLY-3 PERCENT (g) | 7.1% 0.0% 0.0% 0.0% 13.3% | |TERMINAL (d) | 1/14 (7%) 0/15 (0%) 0/15 (0%) 0/15 (0%) 2/15 (13%) | |FIRST INCIDENCE | 189 (T) --- --- --- 189 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.156 P=0.486N P=0.486N P=0.486N P=0.525 | |POLY 3 | P=0.153 P=0.486N P=0.486N P=0.486N P=0.524 | |POLY 1.5 | P=0.153 P=0.486N P=0.486N P=0.486N P=0.524 | |POLY 6 | P=0.153 P=0.486N P=0.486N P=0.486N P=0.524 | |LOGISTIC REGRESSION| P=0.156 (e) (e) (e) P=0.525 | |COCH-ARM / FISHERS | P=0.154 P=0.483N P=0.483N P=0.483N P=0.527 | |ORDER RESTRICTED | P=0.088 (e) (e) (e) (e) | |=================================================================================================================================| Date: 11/05/03 EXPERIMENT: 99034 TEST: 01 Page 12 Statistical Analysis of Non-neoplastic Lesions in Mice(P16(INK4A)/(+/-) (C57BL/6)) - TRANSGENIC MODEL EVALUATION II ( BEN Terminal Sacrifice at 27 weeks |=================================================================================================================================| | | | | | Males | |Dose | 0 MG/KG 25 MG/KG 50 MG/KG 100 200 | | | MG/KG MG/KG | |=================================================================================================================================| | | |Lymph Node, Mesenteric | | Atrophy | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 1/15 (7%) 2/15 (13%) 2/14 (14%) 13/15 (87%) 13/15 (87%) | |POLY-3 RATE (b) | 1/15.00 2/15.00 2/14.00 13/15.00 13/14.00 | |POLY-3 PERCENT (g) | 6.7% 13.3% 14.3% 86.7% 92.9% | |TERMINAL (d) | 1/15 (7%) 2/15 (13%) 2/14 (14%) 13/15 (87%) 13/14 (93%) | |FIRST INCIDENCE | 188 (T) 188 (T) 188 (T) 188 (T) 188 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P<0.001 ** P=0.500 P=0.475 P<0.001 ** P<0.001 ** | |POLY 3 | P<0.001 ** P=0.500 P=0.476 P<0.001 ** P<0.001 ** | |POLY 1.5 | P<0.001 ** P=0.500 P=0.476 P<0.001 ** P<0.001 ** | |POLY 6 | P<0.001 ** P=0.500 P=0.476 P<0.001 ** P<0.001 ** | |LOGISTIC REGRESSION| P<0.001 ** P=0.500 P=0.475 P<0.001 ** P<0.001 ** | |COCH-ARM / FISHERS | P<0.001 ** P=0.500 P=0.473 P<0.001 ** P<0.001 ** | |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 | |=================================================================================================================================| | | |Lymph Node, Mesenteric | | Atrophy | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/15 (0%) 2/15 (13%) 3/15 (20%) 8/15 (53%) 6/15 (40%) | |POLY-3 RATE (b) | 0/15.00 2/15.00 3/15.00 8/15.00 6/15.00 | |POLY-3 PERCENT (g) | 0.0% 13.3% 20.0% 53.3% 40.0% | |TERMINAL (d) | 0/15 (0%) 2/15 (13%) 3/15 (20%) 8/15 (53%) 6/15 (40%) | |FIRST INCIDENCE | --- 189 (T) 189 (T) 189 (T) 189 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.003 ** P=0.236 P=0.116 P=0.002 ** P=0.012 * | |POLY 3 | P=0.002 ** P=0.232 P=0.106 P<0.001 ** P=0.005 ** | |POLY 1.5 | P=0.002 ** P=0.232 P=0.106 P<0.001 ** P=0.005 ** | |POLY 6 | P=0.002 ** P=0.232 P=0.106 P<0.001 ** P=0.005 ** | |LOGISTIC REGRESSION| (e) P=0.236 P=0.116 P=0.002 ** P=0.012 * | |COCH-ARM / FISHERS | P=0.003 ** P=0.241 P=0.112 P<0.001 ** P=0.008 ** | |ORDER RESTRICTED | P<0.001 ** (e) (e) (e) (e) | |=================================================================================================================================| Date: 11/05/03 EXPERIMENT: 99034 TEST: 01 Page 13 Statistical Analysis of Non-neoplastic Lesions in Mice(P16(INK4A)/(+/-) (C57BL/6)) - TRANSGENIC MODEL EVALUATION II ( BEN Terminal Sacrifice at 27 weeks |=================================================================================================================================| | | | | | Males | |Dose | 0 MG/KG 25 MG/KG 50 MG/KG 100 200 | | | MG/KG MG/KG | |=================================================================================================================================| | | |Lymph Node: Mediastinal | | Atrophy | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/11 (0%) 0/11 (0%) 2/12 (17%) 6/9 (67%) 6/7 (86%) | |POLY-3 RATE (b) | 0/11.00 0/11.00 2/12.00 6/9.00 6/7.00 | |POLY-3 PERCENT (g) | 0.0% 0.0% 16.7% 66.7% 85.7% | |TERMINAL (d) | 0/11 (0%) 0/11 (0%) 2/12 (17%) 6/9 (67%) 6/7 (86%) | |FIRST INCIDENCE | --- --- 188 (T) 188 (T) 188 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P<0.001 ** (e) P=0.254 P=0.004 ** P<0.001 ** | |POLY 3 | P<0.001 ** (e) P=0.249 P<0.001 ** P<0.001 ** | |POLY 1.5 | P<0.001 ** (e) P=0.249 P<0.001 ** P<0.001 ** | |POLY 6 | P<0.001 ** (e) P=0.249 P<0.001 ** P<0.001 ** | |LOGISTIC REGRESSION| (e) (e) P=0.254 P=0.004 ** P<0.001 ** | |COCH-ARM / FISHERS | P<0.001 ** (e) P=0.261 P=0.002 ** P<0.001 ** | |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 | |=================================================================================================================================| | | |Lymph Node: Mediastinal | | Atrophy | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/13 (0%) 0/11 (0%) 2/11 (18%) 4/12 (33%) 2/13 (15%) | |POLY-3 RATE (b) | 0/13.00 0/11.00 2/11.00 4/12.00 2/13.00 | |POLY-3 PERCENT (g) | 0.0% 0.0% 18.2% 33.3% 15.4% | |TERMINAL (d) | 0/13 (0%) 0/11 (0%) 2/11 (18%) 4/12 (33%) 2/13 (15%) | |FIRST INCIDENCE | --- --- 189 (T) 189 (T) 189 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.114 (e) P=0.199 P=0.045 * P=0.235 | |POLY 3 | P=0.105 (e) P=0.190 P=0.032 * P=0.230 | |POLY 1.5 | P=0.105 (e) P=0.190 P=0.032 * P=0.230 | |POLY 6 | P=0.105 (e) P=0.190 P=0.032 * P=0.230 | |LOGISTIC REGRESSION| (e) (e) P=0.199 P=0.045 * P=0.235 | |COCH-ARM / FISHERS | P=0.112 (e) P=0.199 P=0.039 * P=0.240 | |ORDER RESTRICTED | P=0.039 * (e) (e) (e) (e) | |=================================================================================================================================| Date: 11/05/03 EXPERIMENT: 99034 TEST: 01 Page 14 Statistical Analysis of Non-neoplastic Lesions in Mice(P16(INK4A)/(+/-) (C57BL/6)) - TRANSGENIC MODEL EVALUATION II ( BEN Terminal Sacrifice at 27 weeks |=================================================================================================================================| | | | | | Males | |Dose | 0 MG/KG 25 MG/KG 50 MG/KG 100 200 | | | MG/KG MG/KG | |=================================================================================================================================| | | |Mammary Gland | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/0 (0%) 0/1 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) | |POLY-3 RATE (b) | 0/0.00 0/1.00 0/0.00 0/0.00 0/0.00 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 0/0 (0%) 0/1 (0%) 0/0 (0%) 0/0 (0%) 0/0 (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 | |=================================================================================================================================| | | |Mammary Gland | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/15 (0%) 0/15 (0%) 0/15 (0%) 0/15 (0%) 2/15 (13%) | |POLY-3 RATE (b) | 0/15.00 0/15.00 0/15.00 0/15.00 2/15.00 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 0.0% 13.3% | |TERMINAL (d) | 0/15 (0%) 0/15 (0%) 0/15 (0%) 0/15 (0%) 2/15 (13%) | |FIRST INCIDENCE | --- --- --- --- 189 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.022 * (e) (e) (e) P=0.236 | |POLY 3 | P=0.019 * (e) (e) (e) P=0.232 | |POLY 1.5 | P=0.019 * (e) (e) (e) P=0.232 | |POLY 6 | P=0.019 * (e) (e) (e) P=0.232 | |LOGISTIC REGRESSION| (e) (e) (e) (e) P=0.236 | |COCH-ARM / FISHERS | P=0.021 * (e) (e) (e) P=0.241 | |ORDER RESTRICTED | P=0.014 * (e) (e) (e) (e) | |=================================================================================================================================| Date: 11/05/03 EXPERIMENT: 99034 TEST: 01 Page 15 Statistical Analysis of Non-neoplastic Lesions in Mice(P16(INK4A)/(+/-) (C57BL/6)) - TRANSGENIC MODEL EVALUATION II ( BEN Terminal Sacrifice at 27 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) | 1/14 (7%) 0/15 (0%) 0/15 (0%) 2/15 (13%) 2/15 (13%) | |POLY-3 RATE (b) | 1/14.00 0/15.00 0/15.00 2/15.00 2/15.00 | |POLY-3 PERCENT (g) | 7.1% 0.0% 0.0% 13.3% 13.3% | |TERMINAL (d) | 1/14 (7%) 0/15 (0%) 0/15 (0%) 2/15 (13%) 2/15 (13%) | |FIRST INCIDENCE | 189 (T) --- --- 189 (T) 189 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.134 P=0.486N P=0.486N P=0.525 P=0.525 | |POLY 3 | P=0.134 P=0.486N P=0.486N P=0.524 P=0.524 | |POLY 1.5 | P=0.134 P=0.486N P=0.486N P=0.524 P=0.524 | |POLY 6 | P=0.134 P=0.486N P=0.486N P=0.524 P=0.524 | |LOGISTIC REGRESSION| P=0.134 (e) (e) P=0.525 P=0.525 | |COCH-ARM / FISHERS | P=0.133 P=0.483N P=0.483N P=0.527 P=0.527 | |ORDER RESTRICTED | P=0.204 (e) (e) (e) (e) | |=================================================================================================================================| Date: 11/05/03 EXPERIMENT: 99034 TEST: 01 Page 16 Statistical Analysis of Non-neoplastic Lesions in Mice(P16(INK4A)/(+/-) (C57BL/6)) - TRANSGENIC MODEL EVALUATION II ( BEN Terminal Sacrifice at 27 weeks |=================================================================================================================================| | | | | | Males | |Dose | 0 MG/KG 25 MG/KG 50 MG/KG 100 200 | | | MG/KG MG/KG | |=================================================================================================================================| | | |Skin | | Pigmentation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/15 (0%) 15/15 (100%) 15/15 (100%) 15/15 (100%) 14/15 (93%) | |POLY-3 RATE (b) | 0/15.00 15/15.00 15/15.00 15/15.00 14/14.00 | |POLY-3 PERCENT (g) | 0.0% 100.0% 100.0% 100.0% 100.0% | |TERMINAL (d) | 0/15 (0%) 15/15 (100%) 15/15 (100%) 15/15 (100%) 14/14 (100%) | |FIRST INCIDENCE | --- 188 (T) 188 (T) 188 (T) 188 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** | |POLY 3 | P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** | |POLY 1.5 | P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** | |POLY 6 | P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** | |LOGISTIC REGRESSION| (e) P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** | |COCH-ARM / FISHERS | P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** | |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 | |=================================================================================================================================| | | |Skin | | Pigmentation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/15 (0%) 1/15 (7%) 8/15 (53%) 15/15 (100%) 15/15 (100%) | |POLY-3 RATE (b) | 0/15.00 1/15.00 8/15.00 15/15.00 15/15.00 | |POLY-3 PERCENT (g) | 0.0% 6.7% 53.3% 100.0% 100.0% | |TERMINAL (d) | 0/15 (0%) 1/15 (7%) 8/15 (53%) 15/15 (100%) 15/15 (100%) | |FIRST INCIDENCE | --- 189 (T) 189 (T) 189 (T) 189 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P<0.001 ** P=0.500 P=0.002 ** P<0.001 ** P<0.001 ** | |POLY 3 | P<0.001 ** P=0.500 P<0.001 ** P<0.001 ** P<0.001 ** | |POLY 1.5 | P<0.001 ** P=0.500 P<0.001 ** P<0.001 ** P<0.001 ** | |POLY 6 | P<0.001 ** P=0.500 P<0.001 ** P<0.001 ** P<0.001 ** | |LOGISTIC REGRESSION| P<0.001 ** P=0.500 P=0.002 ** P<0.001 ** P<0.001 ** | |COCH-ARM / FISHERS | P<0.001 ** P=0.500 P<0.001 ** P<0.001 ** P<0.001 ** | |ORDER RESTRICTED | P<0.001 ** (e) (e) (e) (e) | |=================================================================================================================================| Date: 11/05/03 EXPERIMENT: 99034 TEST: 01 Page 17 Statistical Analysis of Non-neoplastic Lesions in Mice(P16(INK4A)/(+/-) (C57BL/6)) - TRANSGENIC MODEL EVALUATION II ( BEN Terminal Sacrifice at 27 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) | 0/15 (0%) 1/15 (7%) 0/15 (0%) 2/15 (13%) 8/15 (53%) | |POLY-3 RATE (b) | 0/15.00 1/15.00 0/15.00 2/15.00 8/14.00 | |POLY-3 PERCENT (g) | 0.0% 6.7% 0.0% 13.3% 57.1% | |TERMINAL (d) | 0/15 (0%) 1/15 (7%) 0/15 (0%) 2/15 (13%) 8/14 (57%) | |FIRST INCIDENCE | --- 188 (T) --- 188 (T) 188 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P<0.001 ** P=0.500 (e) P=0.236 P<0.001 ** | |POLY 3 | P<0.001 ** P=0.500 (e) P=0.232 P<0.001 ** | |POLY 1.5 | P<0.001 ** P=0.500 (e) P=0.232 P<0.001 ** | |POLY 6 | P<0.001 ** P=0.500 (e) P=0.232 P<0.001 ** | |LOGISTIC REGRESSION| (e) P=0.500 (e) P=0.236 P<0.001 ** | |COCH-ARM / FISHERS | P<0.001 ** P=0.500 (e) P=0.241 P<0.001 ** | |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 | |=================================================================================================================================| | | |Spleen | | Hematopoietic Cell Proliferation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 5/15 (33%) 5/15 (33%) 2/15 (13%) 3/15 (20%) 7/15 (47%) | |POLY-3 RATE (b) | 5/15.00 5/15.00 2/15.00 3/15.00 7/15.00 | |POLY-3 PERCENT (g) | 33.3% 33.3% 13.3% 20.0% 46.7% | |TERMINAL (d) | 5/15 (33%) 5/15 (33%) 2/15 (13%) 3/15 (20%) 7/15 (47%) | |FIRST INCIDENCE | 189 (T) 189 (T) 189 (T) 189 (T) 189 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.211 P=0.648 P=0.198N P=0.342N P=0.357 | |POLY 3 | P=0.210 P=0.646 P=0.195N P=0.343N P=0.358 | |POLY 1.5 | P=0.210 P=0.646 P=0.195N P=0.343N P=0.358 | |POLY 6 | P=0.210 P=0.646 P=0.195N P=0.343N P=0.358 | |LOGISTIC REGRESSION| P=0.211 P=0.648 P=0.198N P=0.342N P=0.357 | |COCH-ARM / FISHERS | P=0.210 P=0.650N P=0.195N P=0.341N P=0.355 | |ORDER RESTRICTED | P=0.156 (e) (e) (e) (e) | |=================================================================================================================================| Date: 11/05/03 EXPERIMENT: 99034 TEST: 01 Page 18 Statistical Analysis of Non-neoplastic Lesions in Mice(P16(INK4A)/(+/-) (C57BL/6)) - TRANSGENIC MODEL EVALUATION II ( BEN Terminal Sacrifice at 27 weeks |=================================================================================================================================| | | | | | Males | |Dose | 0 MG/KG 25 MG/KG 50 MG/KG 100 200 | | | MG/KG MG/KG | |=================================================================================================================================| | | |Spleen: Lymphoid Follicle | | Atrophy | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/15 (0%) 0/15 (0%) 0/15 (0%) 15/15 (100%) 14/15 (93%) | |POLY-3 RATE (b) | 0/15.00 0/15.00 0/15.00 15/15.00 14/14.00 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 100.0% 100.0% | |TERMINAL (d) | 0/15 (0%) 0/15 (0%) 0/15 (0%) 15/15 (100%) 14/14 (100%) | |FIRST INCIDENCE | --- --- --- 188 (T) 188 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P<0.001 ** (e) (e) P<0.001 ** P<0.001 ** | |POLY 3 | P<0.001 ** (e) (e) P<0.001 ** P<0.001 ** | |POLY 1.5 | P<0.001 ** (e) (e) P<0.001 ** P<0.001 ** | |POLY 6 | P<0.001 ** (e) (e) P<0.001 ** P<0.001 ** | |LOGISTIC REGRESSION| (e) (e) (e) P<0.001 ** P<0.001 ** | |COCH-ARM / FISHERS | P<0.001 ** (e) (e) P<0.001 ** P<0.001 ** | |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 | |=================================================================================================================================| | | |Spleen: Lymphoid Follicle | | Atrophy | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/15 (0%) 1/15 (7%) 1/15 (7%) 0/15 (0%) 1/15 (7%) | |POLY-3 RATE (b) | 0/15.00 1/15.00 1/15.00 0/15.00 1/15.00 | |POLY-3 PERCENT (g) | 0.0% 6.7% 6.7% 0.0% 6.7% | |TERMINAL (d) | 0/15 (0%) 1/15 (7%) 1/15 (7%) 0/15 (0%) 1/15 (7%) | |FIRST INCIDENCE | --- 189 (T) 189 (T) --- 189 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.500 P=0.500 P=0.500 (e) P=0.500 | |POLY 3 | P=0.500 P=0.500 P=0.500 (e) P=0.500 | |POLY 1.5 | P=0.500 P=0.500 P=0.500 (e) P=0.500 | |POLY 6 | P=0.500 P=0.500 P=0.500 (e) P=0.500 | |LOGISTIC REGRESSION| (e) P=0.500 P=0.500 (e) P=0.500 | |COCH-ARM / FISHERS | P=0.500 P=0.500 P=0.500 (e) P=0.500 | |ORDER RESTRICTED | P=0.312 (e) (e) (e) (e) | |=================================================================================================================================| Date: 11/05/03 EXPERIMENT: 99034 TEST: 01 Page 19 Statistical Analysis of Non-neoplastic Lesions in Mice(P16(INK4A)/(+/-) (C57BL/6)) - TRANSGENIC MODEL EVALUATION II ( BEN Terminal Sacrifice at 27 weeks |=================================================================================================================================| | | | | | Males | |Dose | 0 MG/KG 25 MG/KG 50 MG/KG 100 200 | | | MG/KG MG/KG | |=================================================================================================================================| | | |Stomach, Forestomach | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 1/15 (7%) 0/15 (0%) 0/15 (0%) 0/15 (0%) 3/15 (20%) | |POLY-3 RATE (b) | 1/15.00 0/15.00 0/15.00 0/15.00 3/15.00 | |POLY-3 PERCENT (g) | 6.7% 0.0% 0.0% 0.0% 20.0% | |TERMINAL (d) | 1/15 (7%) 0/15 (0%) 0/15 (0%) 0/15 (0%) 2/14 (14%) | |FIRST INCIDENCE | 188 (T) --- --- --- 11 | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.033 * P=0.500N P=0.500N P=0.500N P=0.285 | |POLY 3 | P=0.031 * P=0.500N P=0.500N P=0.500N P=0.298 | |POLY 1.5 | P=0.031 * P=0.500N P=0.500N P=0.500N P=0.298 | |POLY 6 | P=0.031 * P=0.500N P=0.500N P=0.500N P=0.298 | |LOGISTIC REGRESSION| P=0.033 * (e) (e) (e) (e) | |COCH-ARM / FISHERS | P=0.035 * P=0.500N P=0.500N P=0.500N P=0.299 | |ORDER RESTRICTED | P=0.014 * (e) (e) (e) (e) | |=================================================================================================================================| | | | | | Females | |Dose | 0 MG/KG 25 MG/KG 50 MG/KG 100 200 | | | MG/KG MG/KG | |=================================================================================================================================| | | |Stomach, Forestomach | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 1/15 (7%) 0/15 (0%) 0/15 (0%) 0/15 (0%) 0/15 (0%) | |POLY-3 RATE (b) | 1/15.00 0/15.00 0/15.00 0/15.00 0/15.00 | |POLY-3 PERCENT (g) | 6.7% 0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 1/15 (7%) 0/15 (0%) 0/15 (0%) 0/15 (0%) 0/15 (0%) | |FIRST INCIDENCE | 189 (T) --- --- --- --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.362N P=0.500N P=0.500N P=0.500N P=0.500N | |POLY 3 | P=0.362N P=0.500N P=0.500N P=0.500N P=0.500N | |POLY 1.5 | P=0.362N P=0.500N P=0.500N P=0.500N P=0.500N | |POLY 6 | P=0.362N P=0.500N P=0.500N P=0.500N P=0.500N | |LOGISTIC REGRESSION| P=0.362N (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=0.087N (e) (e) (e) (e) | |=================================================================================================================================| Date: 11/05/03 EXPERIMENT: 99034 TEST: 01 Page 20 Statistical Analysis of Non-neoplastic Lesions in Mice(P16(INK4A)/(+/-) (C57BL/6)) - TRANSGENIC MODEL EVALUATION II ( BEN Terminal Sacrifice at 27 weeks |=================================================================================================================================| | | | | | Males | |Dose | 0 MG/KG 25 MG/KG 50 MG/KG 100 200 | | | MG/KG MG/KG | |=================================================================================================================================| | | |Stomach, Forestomach | | Inflammation Chronic | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/15 (0%) 0/15 (0%) 0/15 (0%) 0/15 (0%) 0/15 (0%) | |POLY-3 RATE (b) | 0/15.00 0/15.00 0/15.00 0/15.00 0/14.00 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 0/15 (0%) 0/15 (0%) 0/15 (0%) 0/15 (0%) 0/14 (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 | |=================================================================================================================================| | | |Stomach, Forestomach | | Inflammation Chronic | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/15 (0%) 0/15 (0%) 3/15 (20%) 0/15 (0%) 0/15 (0%) | |POLY-3 RATE (b) | 0/15.00 0/15.00 3/15.00 0/15.00 0/15.00 | |POLY-3 PERCENT (g) | 0.0% 0.0% 20.0% 0.0% 0.0% | |TERMINAL (d) | 0/15 (0%) 0/15 (0%) 3/15 (20%) 0/15 (0%) 0/15 (0%) | |FIRST INCIDENCE | --- --- 189 (T) --- --- | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.418N (e) P=0.116 (e) (e) | |POLY 3 | P=0.413N (e) P=0.106 (e) (e) | |POLY 1.5 | P=0.413N (e) P=0.106 (e) (e) | |POLY 6 | P=0.413N (e) P=0.106 (e) (e) | |LOGISTIC REGRESSION| (e) (e) P=0.116 (e) (e) | |COCH-ARM / FISHERS | P=0.417N (e) P=0.112 (e) (e) | |ORDER RESTRICTED | P=0.278 (e) (e) (e) (e) | |=================================================================================================================================| Date: 11/05/03 EXPERIMENT: 99034 TEST: 01 Page 21 Statistical Analysis of Non-neoplastic Lesions in Mice(P16(INK4A)/(+/-) (C57BL/6)) - TRANSGENIC MODEL EVALUATION II ( BEN Terminal Sacrifice at 27 weeks |=================================================================================================================================| | | | | | Males | |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%) 0/15 (0%) 0/15 (0%) 7/15 (47%) 13/15 (87%) | |POLY-3 RATE (b) | 0/15.00 0/15.00 0/15.00 7/15.00 13/14.00 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 46.7% 92.9% | |TERMINAL (d) | 0/15 (0%) 0/15 (0%) 0/15 (0%) 7/15 (47%) 13/14 (93%) | |FIRST INCIDENCE | --- --- --- 188 (T) 188 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P<0.001 ** (e) (e) P=0.005 ** P<0.001 ** | |POLY 3 | P<0.001 ** (e) (e) P<0.001 ** P<0.001 ** | |POLY 1.5 | P<0.001 ** (e) (e) P<0.001 ** P<0.001 ** | |POLY 6 | P<0.001 ** (e) (e) P<0.001 ** P<0.001 ** | |LOGISTIC REGRESSION| (e) (e) (e) P=0.005 ** P<0.001 ** | |COCH-ARM / FISHERS | P<0.001 ** (e) (e) P=0.003 ** P<0.001 ** | |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 | |=================================================================================================================================| | | |Thymus | | Atrophy | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | |----------- | | |OVERALL (a) | 0/15 (0%) 0/15 (0%) 0/15 (0%) 0/15 (0%) 0/15 (0%) | |POLY-3 RATE (b) | 0/15.00 0/15.00 0/15.00 0/15.00 0/15.00 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 0/15 (0%) 0/15 (0%) 0/15 (0%) 0/15 (0%) 0/15 (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: 11/05/03 EXPERIMENT: 99034 TEST: 01 Page 22 Statistical Analysis of Non-neoplastic Lesions in Mice(P16(INK4A)/(+/-) (C57BL/6)) - TRANSGENIC MODEL EVALUATION II ( BEN Terminal Sacrifice at 27 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) | 12/15 (80%) 15/15 (100%) 15/15 (100%) 15/15 (100%) 14/15 (93%) | |POLY-3 RATE (b) | 12/15.00 15/15.00 15/15.00 15/15.00 14/15.00 | |POLY-3 PERCENT (g) | 80.0% 100.0% 100.0% 100.0% 93.3% | |TERMINAL (d) | 12/15 (80%) 15/15 (100%) 15/15 (100%) 15/15 (100%) 14/15 (93%) | |FIRST INCIDENCE | 189 (T) 189 (T) 189 (T) 189 (T) 189 (T) | |-------------------| | |STATISTICAL TESTS | | |-------------------| | |LIFE TABLE | P=0.359 P=0.116 P=0.116 P=0.116 P=0.299 | |POLY 3 | P=0.354 P=0.106 P=0.106 P=0.106 P=0.298 | |POLY 1.5 | P=0.354 P=0.106 P=0.106 P=0.106 P=0.298 | |POLY 6 | P=0.354 P=0.106 P=0.106 P=0.106 P=0.298 | |LOGISTIC REGRESSION| P=0.359 P=0.116 P=0.116 P=0.116 P=0.299 | |COCH-ARM / FISHERS | P=0.358 P=0.112 P=0.112 P=0.112 P=0.299 | |ORDER RESTRICTED | P=0.014 * (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).