酶抑制剂对V79-hCYP2E1-SULT1A1细胞酶依赖性化学诱变的影响  

Effects of enzyme inhibitors on enzyme-dependent and chemical-induced mutagenesis in V79-hCYP2E1-hSULT1A1 cells

作　　者：刘云岗[1] 胡克歧[1] 

机构地区：[1]南方医科大学公共卫生与热带医学学院毒理学系,广州510515

出　　处：《重庆医科大学学报》2011年第9期1029-1032,共4页Journal of Chongqing Medical University

基　　金：广东省高等学校人才引进专项基金资助项目(编号:粤财教[2010]343号)

摘　　要：目的:V79-hCYP2E1-hSULT1A1是一个表达人细胞色素P450(CYP)2E1和硫酸基转移酶(Sulfotransferase,SULT)1A1的重组中国地鼠V79[Chinese hamster lung(V79)cells]细胞系,它对于需有关代谢酶活化的间接诱变剂有基因突变反应;为观察单个酶的作用,需要建立对细胞中任一酶特异抑制的模型。方法:以细胞Hprt位点的正向突变为试验终点,N-二甲基亚硝胺(N-Nitrosodimethylamine,NDMA)和2-硝基丙烷(2-Nitropropane,2-NP)为依赖CYP2E1和SULT1A1的间接诱变剂,观察CYP抑制剂反式二氯乙烯(Trans-1,2-dichloroethylene,DCE)和1-氨基苯并三唑(1-Aminobenzotriazole,ABT)、SULT1抑制剂槲皮素和五氯酚(Pentachlorophenol,PCP)对上述间接诱变剂作用的影响。结果:在一定浓度下,ABT抑制NDMA的诱变率达99%而不影响2-NP的作用,DCE对其抑制仅达55%且对2-NP的细胞毒性有明显加强作用。槲皮素和PCP抑制2-NP的诱变率达63%和98%,且都对NDMA的作用无影响。结论:ABT和PCP可完全且特异地抑制该细胞中CYP2E1和SULT1A1依赖的诱变反应,此模型对于探讨遗传毒物的代谢活化有可靠价值。Objective：V79-hCYP2E1-hSULT1A1,a genetically engineered Chinese hamster V79 cell line expressing human CYP2E1 and human sulfotransferase（SULT）1A1,demonstrates mutagenic response to promutagens requiring metabolic activation by either expressed enzyme.For the purpose of investigating the effect of either enzyme alone,it is highly necessary to establish a test model wherein either of the enzymes is specifically inhibited.Methods：Using the forward mutation at Hprt locus as the end point to observe,N-nitrosodimethylamine（NDMA） and 2-nitropropane（2-NP） as CYP2E1-and SULT1A1-dependent promutagen,the effects of CYP inhibitors,trans-1,2-dichloroethylene（DCE） and 1-aminobenzotriazole（ABT）,and that of SULT1 inhibitors,quercetin and pentachlorophenol（PCP） on each promutagen-induced mutagenic response were observed.Results：ABT prohibited NDMA-induced mutagenic activity by 99% with the action of 2-NP unaffected,while DCE reduced it only by 55% and simultaneously potentiated 2-NP-induced cytotoxicity.Quercetin and PCP reduced 2-NP-induced mutagenic activity by 63% and 98%,with the action of NDMA unaffected.Conclusion：Specifically and completely,ABT and PCP are capable of prohibiting CYP2E1-and SULT1A1-dependent mutagenic response,respectively,which is a test model of reliable value for investigating metabolic activation of genotoxicants.

关 键 词：基因重组细胞 CYP2E1 Hprt位点 酶抑制剂 转硫酸基酶(SULT)1A1 

分 类 号：R114[医药卫生—卫生毒理学]