DNA加合物研究及在环境毒理学中的应用

THE STUDY OF DNA ADDUCTS AND ITS APPLICATION IN ENVIRONMENTAL TOXICOLOGY

致癌物在生物体内经解毒系统诱导与生物体内的DNA形成加合物,DNA加合物综合反映了生物体对致癌物的暴露、吸收、分布、代谢以及机体对DNA的修复能力,是致癌物有效作用的量度,与致癌作用直接相关。目前较多用于DNA加合物测定的方法是^(32)P后标记技术。DNA加合物作为一项反映人群暴露于致癌物的指标在肿瘤分子流行病学研究中得到了较好的应用,鱼与哺乳动物一样可活化致癌物形成DNA加合物,由于解毒系统不完善及DNA修复能力差而对致癌物特别敏感,因此鱼及其他水生动物的DNA加合物研究受到重视并且一直引人注目。

Many genotoxic carcinogens are metabolized to reactive intermediates, which covalently bind to DNA, called DNA adduct. The adducts represent an integration of exposure, absorption, distribution, metabolism, DNA repair, and thus provide a measure of biologically effective dose. The DNA adduct is believed to be involved in carcinogenesis. The major method used in DNA adduct research is r-post labeling technique. As a biomarker for carcinogen exposure, DNA adduct has been applied to tumor molecular epidemiology. Fish have been shown to activate carcinogens to products that form DNA adducts which is the same one described in rodents systems. Furthermore fish is more sensitive to carcinogens due to incomplete detoxification system and limited capacity for DNA repair. Therefore studies of DNA adduct of fish as well as other aquatic animals have received great concern and are still a relative new area. For further consideration in environmental toxicology, more efforts should be focused on establishment of fish as model system in order to facilitate the application of DNA adducts in screening and environmental monitoring of carcinogens or precarcinogen.