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 36(9):1029-1032(2011)
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 36(9):1029-1032(2011) DOI: 10.13406/j.cnki.cyxb.2011.09.002.
Effects of enzyme inhibitors on enzyme-dependent and chemical-induced mutagenesis in V79-hCYP2E1-hSULT1A1 cells
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.