Expression of CYP1A in liver of A/Sn and CC57BR mice differing in sensitivity to hepatocarcinogenesis induced by o-liminoazotoluene

The induction of P450 cytochromes Cyp1a1 and Cyp1a2 in the liver of male mi ce differing in sensitivity to the carcinogenic effect of o-aminoazotoluene (OAT) has been studied. The level of Cyp1a1 and Cyp1a2 mRNA was assayed by quantitative competitive polymerase chain reaction (PCR). In both OAT-trea ted strains, the level of Cyp1a1 mRNA increased more than 1000-fold, while the amount of Cyp1a2 mRNA increased only two- or threefold. Interstrain dif ferences in the Cyp1a mRNA level were revealed. The level of Cyp1a1 mRNA in liver of OAT-induced A/Sn mice was three times higher than in CC57BR mice. The amount of Cyp1a2 mRNA in control and OAT-treated mice was 7 and 13 tim es higher, respectively, than in CC57BR mice. The enzyme activities of cyto chromes P450 la were assayed. An increase in Cyp1a1 mRNA level in OAT-treat ed mice correlated with an enhancement of the benzo[a]pyrene hydrolase and 7-ethoxyresofurin o-deethylase activities; the correlation between the leve l of Cyp1a2 mRNA and 7-ethoxyresofurin o-demethylase activity was much less pronounced. Interstrain variation in Cyp1a1 and Cyp1a2 activities was also shown at the enzyme activity level. We suppose that quantitative differenc es in the Cyp1a2 mRNA level play a key role in OAT-induced hepatocarcinogen esis.