DNA修复酶hMSH2缺陷与细胞遗传不稳定性

hMSH2 deficiency of DNA repair enzyme and cell genetic stability

目的 研究hMSH2酶缺陷与细胞遗传不稳定性的关系。方法 测定hMSH2酶正常细胞HLF与hMSH2酶缺陷细胞人胚肺成纤维细胞 (HLFS)在甲基甲磺酸 (MMS)染毒后的半数抑制浓度 (IC5 0 )、核异常率及微核率。结果 HLF细胞 2 4hIC5 0 约为 7 90 μmol/L ,人胚肺成纤维细胞 (HLFS)细胞 2 4hIC5 0 约为 89 13 μmol/L ;2种细胞的微核率均随染毒剂量的增加而升高 ,且呈正相关 (P <0 0 5) ;2种细胞中、高剂量组与对照组相比 ,微核率均有显著性差异 (P <0 0 5或P <0 0 1) ,而低剂量组均无显著性差异 (P >0 0 5) ;HLFS细胞微核率总体上较HLF细胞高 ,但是 2者之间无显著性差异 (P =0 0 8) ,染毒与转染之间无交互效应。核异常率没有随MMS染毒剂量的增加而升高的趋势 ;不同染毒剂量组HLFS的核异常率均明显高于HLF细胞 (P <0 0 1) ;2种细胞染毒剂量组与对照组相比核异常率在统计学上均无显著性差异 (P >0 0 5)。结论 DNA修复酶hMSH 2缺陷导致烷化耐受、核异常率及微核率增加 。

Objective To study the relationship between hMSH2-deficie ncy and cell genetic instability.Methods After being administered by methyl methanesulphon ate(MMS),50% inhibitory concentration(IC 50 ) of cell viability,rates of abnormal nuclei and that of micronuclei(MN) were detected in HLF and HLFS.Results The IC 50 and HLF to MMS in 24 hours was 7.9 0 ?μmol/L,while that of HLFS was 89.13?μmol/L.Six dose groups of both HLF and HLFS were assessed,in which there were positive dose-effect relationships betwee n the rates of micronuclei and doses( P <0 05).The rates of micronuclei were different significantly( P <0 05 or P <0 01) between middle and high d ose groups v.s control group in either HLF or HLFS.The rates of micronuclei were different significantly between HLF and HLFS in 4?μmol/L and 8?μmol/L group ,while that in 1?μmol/L and 2?μmol/L group showed no difference.The rates of micronuclei in HLFS seem higher than that in HLF,but no statistically significa nt difference was observed,while no interaction between administration and trans fection( P >0 05) was found.In all of the dose groups,the rates of abnormal nuc lei in HLFS were higher significantly than that in HLF( P =0 000).There was n o significant difference in rates of abnormal nuclei between administering group and control group.In total,the rates of abnormal nuclei in HLFS were higher tha n that in HLF significantly( P <0 01).In term of forming abnormal nuclei,the re were no interation between administration and transfection and no dose-effect relationship between rates of abnormal nuclei and doses.Conclusion The hMSH2 deficiency of DNA repair enzyme resu lted in alkylation tolerance,rates of abnormal nuclei and micronuclei increasing ,which suggested that hMSH2 deficiency may increase the cellular genetic instabi lity.