Human CYP2E1-dependent and human sulfotransferase 1A1-modulated induction of micronuclei by benzene and its hydroxylated metabolites in Chinese hamster V79-derived cells

Mutation Research
Hao JiangYungang Liu

Abstract

Benzene is a ubiquitous environmental pollutant and a confirmed human carcinogen, which requires metabolic activation, primarily by CYP2E1, for most of its biological actions. Chromosome damages in benzene-exposed workers and rodents have been observed, and in their urine sulfo- and glucuronide-conjugates of phenol and hydroquinone were present. Yet, direct evidence for human CYP2E1-activated mutagenicity of benzene and the exact significance of phase II metabolism for inactivating benzene metabolites are still missing. In the present study, benzene and its oxidized metabolites (phenol, hydroquinone, catechol, 1,2,4-trihydroxybenzene and 1,4-benzoquinone) were investigated for induction of micronuclei in a V79-derived cell line genetically engineered for expression of both human CYP2E1 and human sulfotransferase (SULT) 1A1 (indicated by active micronuclei induction by 1-hydroxymethylpyrene). The results demonstrated concentration-dependent induction of micronuclei by benzene and phenol, though with lower potency or efficacy than the other metabolites. Inhibition of CYP2E1 by 1-aminobenzotriazole did not change the effect of benzoquinone, but completely abolished that of benzene and phenol, and attenuated that of the other compo...Continue Reading

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Citations

Nov 17, 2015·International Journal of Molecular Sciences·Haiyan WeiYuepu Pu
Nov 15, 2018·International Journal of Environmental Research and Public Health·Zhaodi ManYuepu Pu
Nov 12, 2019·Environmental and Molecular Mutagenesis·Mirjam LuijtenJan van Benthem
Oct 11, 2017·Toxicology Research·Jessica H HartmanJoel N Meyer
Feb 7, 2020·International Journal of Environmental Research and Public Health·Yunqiu PuYuepu Pu
Sep 18, 2016·Mutation Research. Genetic Toxicology and Environmental Mutagenesis·Hansi JiaYungang Liu

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