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 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.
Institute of Toxicology, College of Medicine, National Taiwan University, Taipei, ROC.
R M
RM
Chen
M W
MW
Chou
T H
TH
Ueng
D000818:Animals; D001579:Benzopyrene Hydroxylase / Q000187:drug effects; D002911:Chrysenes / Q000494:pharmacology*; D006224:Cricetinae; D019363:Cytochrome P-450 CYP1A1 / Q000096:biosynthesis*; D004790:Enzyme Induction / Q000187:drug effects; D007668:Kidney / Q000187:drug effects / Q000201:enzymology; D008099:Liver / Q000187:drug effects* / Q000201:enzymology; D008168:Lung / Q000187:drug effects* / Q000201:enzymology; D008297:Male; D008647:Mesocricetus; D009152:Mutagenicity Tests; D009601:Nitroreductases / Q000187:drug effects
D002911:Chrysenes; C035986:6-nitrochrysene; D001579:Benzopyrene Hydroxylase; D019363:Cytochrome P-450 CYP1A1; C037214:1-nitropyrene reductase; D009601:Nitroreductases