title: Induction of CYP1A1, 2B, 2E1 and 3A in rat liver by organochlorine pesticide dicofol.
abstract: The present study has determined the ability of dicofol, an organochlorine pesticide, to induce cytochrome P450 using rats treated with 1, 10, and 25mg/kg dicofol intraperitoneally for 4 days. Treatments with 10 and 25mg/kg dicofol produced dose-related increases of cytochrome P450 and cytochrome b(5) contents and NADPH-cytochrome c reductase, 7-ethoxyresorufin O-deethylase, pentoxyresorufin O-dealkylase, aniline hydroxylase, and erythromycin N-demethylase activities in liver microsomes. The treatments also increased glutathione S-transferase and superoxide dismutase activities in liver cytosol. Dicofol at 1mg/kg produced a general trend towards increases of the aforementioned enzyme levels. The results of immunoblot analyses showed that 10 and 25mg/kg dicofol increased protein levels of CYP1A1, CYP2B, CYP2E1, and 3A in liver. RT-PCR data indicated that dicofol induced mRNA expression of liver CYP1A1, CYP2B, and CYP3A. Pretreatments of rats with 10 and 25mg/kg dicofol decreased phenobarbital-induced sleeping time by 34% and 39%, respectively. Dicofol pretreatment at 25mg/kg increased CCl4-induced serum alanine aminotransferase activity by 4.3-fold and aspartate aminotransferase activity by 4.1-fold. The present study demonstrates that dicofol has the ability to induce CYP1A1, CYP2B, CYP2E1, and CYP3A in the liver and increase phenobarbital metabolism and CCl4 toxicity in rats.
authors: Institute of Toxicology, College of Medicine, National Taiwan University, 1 Jen Ai Road, Section 1, Taipei, Taiwan, ROC.
authors: Wei-Hung
authors: WH
authors: Chan
authors: Jiunn-Wang
authors: JW
authors: Liao
authors: Chen-Ping
authors: CP
authors: Chou
authors: Ping-Kun
authors: PK
authors: Chan
authors: Chung-Fan
authors: CF
authors: Wei
authors: Tzuu-Huei
authors: TH
authors: Ueng
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002251:Carbon Tetrachloride / Q000494:pharmacology; D002384:Catalysis; D056486:Chemical and Drug Induced Liver Injury / Q000201:enzymology / Q000473:pathology; D021983:Cyclophilins / Q000494:pharmacology; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis* / Q000378:metabolism; D004010:Dicofol / Q000494:pharmacology*; D004591:Electrophoresis, Polyacrylamide Gel; D004790:Enzyme Induction / Q000187:drug effects; D007306:Insecticides / Q000494:pharmacology*; D007527:Isoenzymes / Q000096:biosynthesis / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000201:enzymology* / Q000473:pathology; D008297:Male; D010634:Phenobarbital / Q000494:pharmacology; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012890:Sleep / Q000187:drug effects
chemical_list: D007306:Insecticides; D007527:Isoenzymes; D012333:RNA, Messenger; D003577:Cytochrome P-450 Enzyme System; D002251:Carbon Tetrachloride; D021983:Cyclophilins; D004010:Dicofol; D010634:Phenobarbital