Induction of cytochrome P450 1A in hamster liver and lung by 6-nitrochrysene |
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Authors: | Ruei-Ming Chen Ming W. Chou Tzuu-Huei Ueng |
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Affiliation: | (1) Institute of Toxicology, College of Medicine, National Taiwan University, 1 Jen Ai Road, Section 1, Taipei, Taiwan, ROC, TW;(2) National Center for Toxicological Research, Jefferson, Arkansas, USA, US |
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Abstract: | The present study has determined the effect of 6-nitrochrysene (6-NC) on hepatic and pulmonary cytochrome P450 (P450)-dependent monooxygenases using hamsters pretreated with the nitrated polycyclic aromatic hydrocarbon (nitro-PAH) at 5 mg/kg per day for 3 days. Pretreatment with 6-NC elevated serum gamma-glutamyltranspeptidase, lactate dehydrogenase, and bilirubin levels. Liver S9 fractions prepared from controls and hamsters pretreated with 6-NC markedly increased mutagenicity of the nitro-PAH in Salmonella typhimurium tester strains TA98, TA100, and TA102. The pretreatment selectively increased 1-nitropyrene reductase activities of lung cytosol and liver and lung microsomes. Pretreatment with 6-NC resulted in increases of microsomal 7-ethoxyresorufin and methoxyresorufin O-dealkylases activities in liver and lung without affecting the monooxygenase activities in kidney. Immunoblot analysis of microsomal proteins using mouse monoclonal antibody 1–12–3 to rat P450 1A1 revealed that 6-NC induced P450 1A-immunorelated proteins in liver and lung. RNA blot analysis using mouse P450 1A1 cDNA showed that 6-NC increased liver and lung P450 1A mRNA. 6-NC had no effect on the kidney P450 protein and mRNA. The present study demonstrates that the hamster enzymes can support 6-NC metabolic activation and the nitro-PAH induces liver and lung P4501A via a pretranslational mechanism. Received: 5 January 1998 / Accepted: 25 February 1998 |
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Keywords: | 6-Nitrochrysene Cytochrome P450 Mutagenicity Nitroreductase |
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