New trend in genotoxicity research taking into account genome instability

Abstract

Since mutagenicity which can induce permanent transmissible changes in the structure of the genetic material is one of the major causes of cancer, research for genotoxicity including mutagenicity has focused on cancer hazard identification. Thus, it has been assumed that there was no threshold in mutagenesis. On the other hand, tumor development induced by not only non-genotoxic carcinogen but also genotoxic carcinogens will likely show a practical threshold. Therefore, statistical evaluation can provide value of the benchmark dose lower confidence limit (BMDL) calculated by approaches for the determination of genetic toxicity point of departure (PoD). In addition, disruption of epigenetic regulation which affect transcription through alteration of chromatin structure is considered to be important in future genotoxicity research. Taking into account benchmark dose or epigenetics will help improve assessment of genotoxicity, which offer promising insight into understanding genomic instability. Overall, this review presents current trends for future assessments of genotoxicity.