氯化镉对V79细胞hprt基因位点突变频率的影响及锌的作用

Study on Mutagenicity of CdCl_2 on hprt loci and Inhibitive Effects of ZnCl_2 in vitro

目的了解氯化镉(CdCl2)对中国仓鼠肺成纤维细胞(V79细胞)hprt基因位点突变频率的影响及锌的拮抗作用,探讨镉的遗传毒性机制。方法采用克隆形成法了解CdCl2对V79细胞的慢性毒性作用;在此基础上采用克隆法研究不同浓度CdCl2对V79细胞hprt基因位点突变频率的影响,并采用生理浓度的氯化锌(ZnCl2)与CdCl2同时作用后,观察锌对于镉致突变效应的影响。同时观察不同浓度CdCl2预先染毒24 h后,对过氧化氢(H2O2)所致hprt基因位点突变效应的影响及锌的拮抗作用。结果克隆形成实验中,CdCl2对V79细胞的毒性随染毒浓度增加而增高,呈线性关系;CdCl2可以引起V79细胞hprt基因位点突变频率增加,在0.1和8μmol/L染毒浓度处分别有两个峰值。CdCl2与H2O2联合作用表现为协同效应。ZnCl2可以拮抗这种效应。结论在本实验条件下,CdCl2可以导致V79细胞hprt基因位点突变,并可使其他致突变物的致突变性增强,而锌可以拮抗此效应。

Objective To investigate hprt mutation frequency in Chinese hamster lung fibroblast cells （V79） exposed to CdCl2 and the inhibition of ZnCl2, and to explore the cytogenetic mechanism of Cd. Methods Clone formation assay was used to detect the cytotoxicity of CdCl2 on V79 cells line and to observe the effects induced by CdCl2 alone or with hydcogen peroxide on hprt locus. 10μmol/L ZnCl2 was used as an inhibitor. Results Different dosage of CdCl2 could effectively lower the clone ability after treatment for 24 h; the effect was in a dose-dependent manner. CdCl2 could increase the hprt mutation frequency in V79 cells with two peak values, which were at 0. 1 and 8μmol/L respectively. Synergetic effects were found in the combined treatment of CdCl2 and H2O2, while 10μmol/L ZnCl2 could protect ceils from effects of CdCl2 on clony forming ability and hprt locus. Conclusions CdCl2 alone could result in mutation of the hprt loci in V79 cells; it could also increase the mutagenicity of H2O2, while ZnCl2 could antagonize all these effects.