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 monooxygenas es using hamsters pretreated with the nitrated polycyclic aromatic hyd rocarbon (nitro-PAH) at 5 mg/kg per day for 3 days. Pretreatment with 6-NC elevated serum gamma-glutamyltranspeptidase, lactate dehydrogenas e, 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 TA 102. The pretreatment selectively increased l-nitropyrene reductase ac tivities of lung cytosol and liver and lung microsomes. Pretreatment w ith 6-NC resulted in increases of microsomal 7-ethoxyresorufin and met hoxyresorufin O-dealkylases activities in liver and lung without affec ting the monooxygenase activities in kidney. Immunoblot analysis of mi crosomal proteins using mouse monoclonal antibody 1-12-3 to rat P450 1 A1 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 kidn ey P450 protein and mRNA. The present study demonstrates that the hams ter enzymes can support 6-NC metabolic activation and the nitro-PAH in duces liver and lung P4501A via a pretranslational mechanism.