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遗传毒性评价研究在药物研发中起着非常重要的作用,但是遗传毒性试验的假阳性和/或假阴性结果会干扰对候选药物利弊权衡的决策,因此对体外、体内遗传毒性试验结果进行正确的综合分析尤为重要。本文就遗传毒性标准试验组合中影响结果分析评价的若干争议热点,如体外哺乳动物细胞试验的高阳性率、代谢因素、体内微核试验的影响因素等研究进展进行综述,概括结果分析和追加试验流程图,并对遗传毒性标准试验组合的完善提出一些展望,为遗传毒理指导原则的修订完善和遗传毒性评价工作的深入开展提供指导线索。
Genotoxicity evaluation studies play a very important role in drug development, but false positives and / or false negatives of genotoxicity tests can interfere with the tradeoffs between the pros and cons of drug candidates and therefore justify in vitro and in vivo genotoxicity testing Comprehensive analysis is particularly important. In this paper, several controversial hotspots affecting the evaluation of results in the genotoxicity standard test combination are reviewed, such as the high positive rate of in vitro mammalian cell tests, metabolic factors, influencing factors of in vivo micronucleus test and so on. The generalized result analysis and additional test Flow chart, and put forward some prospects for the perfection of the standard test combination of genotoxicity, and provide clues for the revision and perfection of the guiding principles of genotoxicity and the further development of genotoxicity evaluation.