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Effects of Cigarette Smoke Condensate on the Activities of Xenobiotic Metabolizing Enzymes in Primary Cultured Rat Hepatocytes  

Park, Mi-Jung (Department of Visual Optics, Seoul National Univeristy of Technology)
Song, Yeon-Jung (Institute of Bioscience & Biotechnology, Daewoong Pharm Co. LTD)
Seo, Kyung-Won (Department of Drug Evaluation, Korea Food and Drug Administration)
Publication Information
Biomolecules & Therapeutics / v.12, no.3, 2004 , pp. 185-188 More about this Journal
Abstract
The purpose of this study is to evaluate the effect of cigarette smoke condensate (CSC) on toxification/detoxification metabolic pathway in primary cultured rat hepatocytes. We measured the activities of cytochrome P450 monooxygenases (CYP450s) and UDP-glucuronyltransferase, sulfotransferase and glutathione-S-transferase in CSC-treated rat hepatocytes. CSC significantly increased the activities of hepatic CYP4501A1 and CYP4501A2 to 7.5 fold and 1.6 fold respectively, compared with control level. However, CSC did not affect the activities of conjugation enzymes. We a1so examined if treatment of CSC could change thc cytotoxicity of acetaminophen (AA) through modulation of metabolizing enzymes. In rat hepatocytes, pretreatment with CSC potentiated the cytotoxicity of AA. This result indicates that potentiation of AA toxicity by CSC pretreatment may be related to induction of CYP4501A1 and CYP4501A2.
Keywords
cigarette smoke condensate; metabolizing enzymes; acetaminophen;
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