Induction of cytochrome P450 1A in hamster liver and lung by 6-nitrochrysene

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...

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Bibliographic Details
Published in:Archives of toxicology 1998-06, Vol.72 (7), p.395-401
Main Authors: CHEN, R.-M, CHOU, M. W, UENG, T.-H
Format: Article
Language:English
Subjects:
Animals
Benzopyrene Hydroxylase - drug effects
Biological and medical sciences
Chemical and industrial products toxicology. Toxic occupational diseases
Chrysenes - pharmacology
Cricetinae
Cytochrome P-450 CYP1A1 - biosynthesis
Enzyme Induction - drug effects
Kidney - drug effects
Kidney - enzymology
Liver - drug effects
Liver - enzymology
Lung - drug effects
Lung - enzymology
Male
Medical sciences
Mesocricetus
Mutagenicity Tests
Nitroreductases - drug effects
Toxicology
Various organic compounds
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Summary: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.
ISSN:0340-5761
1432-0738
DOI:10.1007/s002040050519