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https://ntp.niehs.nih.gov/go/35896

Toxicogenomics

Scientists working with cell cultures under sterile hood

Study Overview

Study: Toxicogenomics
Species: Rats, mice

Description

Toxicogenomic studies evaluate the role of the genome and its related entities in the manifestation of xenobiotic-induced toxicity and disease. Biological samples may be from in vitro or in vivo studies.

Toxicogenomic studies evaluate a wide range of molecular endpoints, including:

  • Epigenomes (e.g., ChIP-chip, bisulfate sequencing)
  • Genomes (e.g., SNP microarrays, CGH microarrays, next generation sequencing)
  • Metabolomes (e.g., GC-MS, LC-MS, NMR)
  • Proteomes (e.g., MS based proteomics, antigen profiling, cytokine arrays)
  • Transcriptomes (e.g., microarray, RNA-seq, RT-PCR, nanobead arrays, RNAi, SAGE analysis)

5-Day Rodent Toxicogenomic Studies

This screening level study type is designed to broadly query the effect of substances on molecular biological processes. The patterns of change produced at the genomic level can be used to forecast the potential toxicological properties of the substance being studied. In 5-day toxicogenomic studies, substances are tested in rats or mice at a wide range of dose levels for their potential to cause changes in gene expression in selected target organs. Target organs are selected based on a variety of considerations, including:

  • Previous studies of the substance or structurally similar chemical
  • Computational prediction of toxicity based on chemical structure
  • Knowledge of the general susceptibility of the organ system to chemical toxicity

Dosing is typically done by introducing the substance directly into the stomach of rodents to ensure accurate dosing over the short study duration. Rodents are exposed to the substance starting at 6-8 weeks of age, receiving 1 dose per day for 5 days, or a total of 5 doses. Depending on the characteristics of the substance, the exposure period may be modified. The rodents are monitored throughout the study for signs of toxicity.

At necropsy, samples of the target organs are taken and processed for genomic analysis. The resulting genomic data are compared to the data for untreated animals to identify any possible effects on molecular biological processes. The genomic data also undergo dose-response modeling to identify the doses of the substance that produce no change in molecular biological processes. Additional biological samples may be used for evaluation for metabolomics, clinical chemistry, hematology, and erythrocyte micronucleus.