ABSTRACT
Over the past several decades, it has been shown that the correlation between genotoxicity, the induction of mutation and/or chromosomal damage, and carcinogenicity is complicated by additional nongenotoxic mechanisms of carcinogenesis and the limitations of in vitro genetic toxicity assays and endpoints. Because of the nature of genetic toxicity assays that provide only a limited insight into genotoxic mechanisms, it is often diffi cult to assess risk and relevance of the positive fi ndings in the in vitro assays to humans. Indeed, for
1. INTRODUCTION 207 2. TRANSCRIPTOMICS 209 2.1. Application of Transcriptomics in Genetic Toxicology
and Evaluating Chemical Carcinogenesis 211 2.2. Advantages and Challenges of Transcriptomics-Based Approaches 213 3. FUNCTIONAL GENOMICS 215 4. SUMMARY 217 REFERENCES 217
marketed drugs with negative carcinogenicity bioassays but positive genotoxicity fi ndings, the majority of positive genotoxicity fi ndings were obtained from in vitro mammalian mutation and/or chromosome damage assays ( 4 ). Therefore, the interpretation and risk assessment of positive fi ndings in the in vitro mammalian mutation and/or chromosome damage assays is a major challenge to both industry and regulatory agencies.
