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

Ruei Ming Chen, Ming W. Chou, Tzuu Huei Ueng

Research output: Contribution to journalArticle

32 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)395-401
Number of pages7
JournalArchives of Toxicology
Volume72
Issue number7
DOIs
Publication statusPublished - 1998
Externally publishedYes

Keywords

  • 6-Nitrochrysene
  • Cytochrome P450
  • Mutagenicity
  • Nitroreductase

ASJC Scopus subject areas

  • Toxicology
  • Health, Toxicology and Mutagenesis

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