Song, Mi-Kyung Kim, Youn-Jung Song, Mee Choi, Han-Seam Park, Yong-Keun Ryu, Jae-Chun 2024-01-20T15:05:32Z 2024-01-20T15:05:32Z 2021-09-05 2012-03 1382-6689 https://pubs.kist.re.kr/handle/201004/129466 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. (C) 2011 Elsevier B.V. All rights reserved. English ELSEVIER SCIENCE BV POLYCYCLIC AROMATIC-HYDROCARBONS DNA-DAMAGE MOUSE SKIN CELLULAR GROWTH GENE-EXPRESSION G(1) ARREST HEPG2 CELLS P38 MAPK ACTIVATION ADDUCTS 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 Article 10.1016/j.etap.2011.12.020 1 ENVIRONMENTAL TOXICOLOGY AND PHARMACOLOGY, v.33, no.2, pp.212 - 225 ENVIRONMENTAL TOXICOLOGY AND PHARMACOLOGY 33 2 212 225 scie scopus 000301475000012 2-s2.0-84862789593 Environmental Sciences Pharmacology & Pharmacy Toxicology Environmental Sciences & Ecology Pharmacology & Pharmacy Toxicology Article POLYCYCLIC AROMATIC-HYDROCARBONS DNA-DAMAGE MOUSE SKIN CELLULAR GROWTH GENE-EXPRESSION G(1) ARREST HEPG2 CELLS P38 MAPK ACTIVATION ADDUCTS Benz[a]anthracene Cytochrome P450 Aldo-keto reductase Benz[a]anthracene-3,4-diol-1,2-epoxide Cytotoxicity Genotoxicity