氧化应激与化合物非遗传毒性致癌性的研究进展

癌症是严重威胁人类健康与生命的一类疾病，致癌性评价已成为新药上市前安全性评价的重要环节，然而，当前可以检出非遗传毒性致癌物的手段十分有限，只有深入挖掘致癌物的作用机制，才能更好地开发相应的检测方法。非遗传毒性致癌物的致癌机制广泛而复杂，氧化应激作用是其中重要的作用机制之一。生理状态下，细胞内的活性氧（reactive oxygen species，ROS）对氧化还原调节及生物信息的传递具有至关重要的作用，然而在氧化应激条件下，ROS在癌症的启动、促癌和发展过程中均扮演着重要角色，并通过诱导脂质、蛋白质、DNA氧化损伤和调控基因表达2种方式发挥非遗传毒性致癌性。本文就氧化应激与非遗传毒性致癌物致癌机制的研究进展进行综述，为抗氧化剂和抗癌药物的开发，探索较为灵敏的非遗传毒性致癌物毒性生物标志物和新型检测手段提供借鉴，为药物致癌性评价提供有益参考。

Cancer is a class of diseases which could seriously treat the health and life of human being,and the carcinogenicity evaluation has become an important component of the preclinical safety evaluation of drugs. However,at present,the methods for detecting non-genotoxic carcinogens are very limited,and further investigation on the mechanisms of carcinogens is the only way for exploring better detection methods. The mechanisms of non-genotoxic carcinogens in inducing cancers are complicated and comprehensive,and oxidative stress is one of the significant mechanisms.Under physiological condition,intracellular ROS has a vital impact on regulating redox reaction and transfering information. ROS plays a crucial role in the process including initiation progress and promotion progress. Oxidative stress could cause cancer through oxidative protein damage,lipid damage,DNA damage or/and modulation of gene expression. In this review,the progress of oxidative stress and the carcinogenesis of non-genotoxic carcinogens are discussed,to aid the developments of antioxidants and anticancer drugs,and provide useful references for identifying sensitive toxicity biomarkers and novel detection methods of non-genotoxic carcinogens,which will be beneficial to the carcinogenicity evaluation of drugs.