遗传毒性标准试验组合结果分析的最新进展

Progress in analysis of findings in the standard battery of genotoxicity tests

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 research plays an important role in new drug development,but the false positive and/or false negative results of genotoxicity tests may interfere weighing the risks of candidate drugs and making decisions.Thus it is particularly important to give comprehensive and sound analysis of these in vitro and in vivo findings.In this review,we summarized the major research progress about some controversial hot spots that influence the analysis and evaluation of the findings in the standard battery of genotoxicity tests,such as the high rate of positive results in in vitro mammalian cell tests,metabolic considerations,the influence factors about in vivo micronucleus studies and so on.The recommendation frameworks for interpretation of standard battery and follow-up test were also included.Finally the prospect of some improvements to the standard battery of genotoxicity tests was put forward.These may provide some key clues for the revision of existing guidelines for genotoxicity and the development of genetic toxicity assessment work.