Development of a single DNA adduct-caused gene mutation assay as a model of low-dose exposure

点击翻译按钮获取中文摘要

Conventional technique of investigating an influence of low-dose exposure, commonly extrapolated from high-dose to low-dose region in Toxicology, is limited. Then, we have developed a new experimental system as a model of low-dose exposure, which can be used to determine the mutagenicity of synthetic DNA adducts at exon5 of thymidine kinase gene in human lymphoblastoid TSCER122 cells, derived from TK6 cell line. As a result, when an adduct forms at least one molecule on genomic DNA, it can cause gene mutation. The observation supports the idea that genotoxic carcinogens have no thresholds for the cancer risk. However, DNA repair functions in this experimental system do not work properly. In order to confirm the existence of threshold, it is necessary to study in detail the mechanisms of a single DNA adduct-caused gene mutation using TSCER122 cells knocked out DNA repair genes.