哺乳类细胞非定标性突变机制的研究

STUDY ON MECHANISMS OF NONTARGETED MUTAGENESIS IN MAMMALIAN CELLS

非定标性突变是发生在DNA损伤剂攻击部位之外的突变，其在哺乳类细胞的形成机制是一个亟待解决的课题。本文作为系统研究的一部分，首先观察化学诱变剂甲基硝基硝胍（MNNG）引起的非洲绿猴肾vero细胞非定标性突变率的时相变化，继而在突变率最高时点分别以RNA合成抑制剂和蛋白质合成抑制剂阻断基因转录和翻译，结果发现前者能使MNNG引起的非定标突变率下降到对照水平，而后者反而使突变率大大增高。提示非定标性突变形成过程中可能发生基因表达改变，并提出引起这种改变的细胞信号传导通路假设和今后的研究方向。

Nontargeted mutagenesis refers to the mutagenesis that happens to undamaged base sites of DNA, its mechanisms in mammalian cells remain to be verdied. In this research (part of a series of rcseaehes ), the dynamic characteristic of nontargeted mutagenesis induced with chemical mutagen MNNG in African green monkey kidney vero cells was illustrated first, then followed by blocking gene transcription and translation with RNA and protein sruthetic inhibitorrespetively at the time point that generated the hishest level of nontargeted mutation. The results show that the former mutation frequency decline to control level as the transcription blocked, while the latter rise remarkably when the translation blocked. In conclusion, the research reeds the possibility that changes in gene expressi on inrolve in the course of nontargeted mutagenesis and hints the hypothesis of the signal transduction pethways wih the mutagenesis in cells which has yet to be proved.