Preferential induction of the rat hepatic P450 I proteins by the food carcinogen 2‐amino‐3‐methyl‐imidazo[4,5‐f]quinoline

Abstract

1 Administration of the food carcinogen, 2‐amino‐3‐methyl‐imidazo[4,5‐f]quinoline (IQ) to rats gave rise to significant dose‐dependent increases in the microsomal O‐deethylations of ethoxycoumarin and ethoxyresorufin but had no effect on the O‐dealkylation of pentoxyresorufin and the NADPH‐dependent reduction of cytochrome c, and decreased the N‐demethylation of dimethylnitrosamine. Microsomal cytochrome b₅ and total cytochrome P‐450 levels decreased following the administration of the carcinogen. 2 Hepatic microsomal preparations from IQ‐treated animals were much more efficient than control in activating the premutagen 2‐amino‐6‐methyldipyrido[1,2‐a:3′,2′‐d]imidazole to mutagenic intermediates in the Ames test. 3 Immunoquantification of two of the major families of cytochrome P‐450, namely P450 I and P450 II B, using ELISA techniques showed that treatment with IQ induced the apoprotein levels of the P450 I family but not of P450 II B. 4 Immunoblot analysis employing polyclonal antibodies against P450 I revealed that IQ induced both isoenzymes of this family, namely P450 I A1 and A2. 5 It is concluded that IQ is an inducer of the rat hepatic monooxygenases, selectively inducing the P450 I family as predicted by a computer‐graphic analysis of its dimensions which showed that it is a large, essentially planer, molecule.