Formation of a 3,4-diol-1,2-epoxide metabolite of benz[a]anthracene with cytotoxicity and genotoxicity in a human in vitro hepatocyte culture system

Title
Formation of a 3,4-diol-1,2-epoxide metabolite of benz[a]anthracene with cytotoxicity and genotoxicity in a human in vitro hepatocyte culture system
Authors
송미경Youn-Jung Kim송미최한샘Yong-Keun Park류재천
Keywords
Benz[a]anthracene; Cytochrome P450; Aldo-keto reductase; Benz[a]anthracene-3,4-diol-1,2-epoxide; Cytotoxicity; Genotoxicity
Issue Date
2012-03
Publisher
Environmental toxicology and pharmacology
Citation
VOL 33, NO 2, 212-215
Abstract
Polycyclic aromatic hydrocarbons (PAHs) are environmental pollutants that require metabolic activation to exert their carcinogenic effects. This study investigated the 3,4-diol-1,2-epoxide formation of benz[a]anthracene (BA) and its toxic effects in a human in vitro hepatocyte culture system. Both mRNA and protein expression of metabolic enzymes which can activate PAHs to carcinogenic forms increased after BA exposure in HepG2 cells and our quantitative analysis showed that the formation of BA-3,4-diol-1,2-epoxide in medium extracts increased in a time-dependent manner. We also performed several comparative studies which show that much lower concentrations of BA-3,4-diol-1,2-epoxide had stronger cytotoxicity and genotoxicity than higher doses of BA. These results suggest that BA is activated as the major carcinogenic metabolite 3,4-diol-1,2-epoxide, in human in vitro culture systems by metabolic enzymes and that this metabolite has stronger cytotoxic and genotoxic effects than its parent compound.
URI
http://pubs.kist.re.kr/handle/201004/44083
ISSN
13826689
Appears in Collections:
KIST Publication > Article
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