Induction of murine CYP1A2 gene expression by acenaphthylene

Abstract

Acenaphthylene and related polynuclear aromatic hydrocarbons (PAH) are industrial combustion by-products which are also found in cooked foods. Recent studies in this laboratory have shown that acenaphthylene induces Cypla2 gene expression in mice and this study further investigates this induction response. Studies with six genetically-inbred strains of mice have shown that the activity of acenaphthylene (300 mg/kg) as an inducer of CYPlA2-dependent methoxyresorufin 0-demethylase (MROD) was age-and strain-dependent. The results showed that DBA mice, compared to the C57BL/6, C3H, CBA, A/j and SJL strains were most responsive to induction after a single dose of acenaphthylene (300 mg/kg). Hepatic MROD activity in acenaphthylene-treated DBA mice was induced 22-and 4-fold in males and females respectively. In contrast, a <2 to 4-fold induction of ethoxyresorufin 0-deethylase (EROD) activity was observed in both sexes. The other inbred strains had higher basal rates of hepatic MROD activity than the DBA strain, (i.e. C3H, C57BL/6, CBA, A/j and SJL). Differences in induction of MROD activity by acenaphthylene among the strains was primarily due to allelic variation (responsive or non responsive) at the aryl hydrocarbon (Ah) locus. Current studies are focused on further characterizing the strain-specific effects of acenaphthylene and related compounds and the molecular regulation of hepatic CYPlA2 gene expression in male and female DBA mice and other rodent species.