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南方医科大学公共卫生与热带医学学院毒理学系
纸质出版日期:2011,
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[1]刘云岗,胡克歧.酶抑制剂对V79-hCYP2E1-SULT1A1细胞酶依赖性化学诱变的影响[J].重庆医科大学学报,2011,36(09):1029-1032.
LIU Yun-gang, HU Ke-qi. Effects of enzyme inhibitors on enzyme-dependent and chemical-induced mutagenesis in V79-hCYP2E1-hSULT1A1 cells[J]. Journal of Chongqing Medical University, 2011,36(9):1029-1032.
[1]刘云岗,胡克歧.酶抑制剂对V79-hCYP2E1-SULT1A1细胞酶依赖性化学诱变的影响[J].重庆医科大学学报,2011,36(09):1029-1032. DOI: 10.13406/j.cnki.cyxb.2011.09.002.
LIU Yun-gang, HU Ke-qi. Effects of enzyme inhibitors on enzyme-dependent and chemical-induced mutagenesis in V79-hCYP2E1-hSULT1A1 cells[J]. Journal of Chongqing Medical University, 2011,36(9):1029-1032. DOI: 10.13406/j.cnki.cyxb.2011.09.002.
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.
基因重组细胞CYP2E1Hprt位点酶抑制剂转硫酸基酶(SULT)1A1
genetically engineered cellsCYP2E1hprt locusenzyme inhibitorsulfotransferase(SULT)1A1
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