Please use this identifier to cite or link to this item: http://hdl.handle.net/11455/33149
標題: Induction and inhibition of cytochrome P450-dependent monooxygenases of rats by fungicide bitertanol
作者: Chan, P.K.
廖俊旺
Lu, S.Y.
Liao, J.W.
Wei, C.F.
Tsai, Y.Y.
Ueng, T.H.
關鍵字: bitertanol
induction
inhibition
CYP1A1
CYP2B
CYP3A
polymerase-chain-reaction
gene-expression
monoclonal-antibodies
liver
microsomes
breast-cancer
assay
glutathione
metabolism
substrate
proteins
期刊/報告no:: Food and Chemical Toxicology, Volume 44, Issue 12, Page(s) 2047-2057.
摘要: The effects of fungicide bitertanol on cytochrome P450-dependent monooxygenases were studied using rats treated intraperitoneally with the N-substituted triazole for 4 days. Treatment with 10, 25, and 100 mg/kg bitertanol produced 2-, 4-, and 14-fold increases of 7-ethoxyresorufin O-deethylation activity in liver microsomes, respectively. Immunoblot analysis of microsomal proteins revealed that 25 mg/kg bitertanol increased CYP1A1 protein in the liver, kidney, and lung by 10-, 13-, and 17-fold, respectively. Bitertanol produced smaller increases of CYP2B and CYP3A catalytic activity and protein than that of CYP1A1 in liver. RT-PCR analysis of total RNA indicated that bitertanol-induced CYP1A1, CYP2B, and CYP3A mRNA. Additions of 0.01-100 mu M bitertanol to liver microsomes from rats treated with 25 mg/kg bitertanol or 3-methylcholanthrene inhibited microsomal 7-ethoxyresorufin O-deethylation activity (IC50 = 0.8 or 0.9 mu M). Bitertanol at 100 mg/kg increased liver UDP-glucuronosyltransferase and glutathione S-transferase activities by 2-fold. Bitertanol at 25 mg/kg produced a minor increase in metabolic activation of benzo[a]pyrene by liver S-9 fraction in the Ames mutagenicity test while the increase was blocked by addition of 100 mu M bitertanol. These findings show that bitertanol is an inducer of CYP1A1, CYP2B, and CYP3A in vivo and an inhibitor of CYP1A catalytic activity in vitro. (c) 2006 Elsevier Ltd. All rights reserved.
URI: http://hdl.handle.net/11455/33149
ISSN: 0278-6915
文章連結: http://dx.doi.org/10.1016/j.fct.2006.07.005
Appears in Collections:獸醫病理生物學所

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