1. Administration of the food carcinogen, 2-amino-3-methyl-imidazo[4,5-flquinoline (IQ) to rats gave rise to significant dose-dependent increases in the microsomal 0-deethylations of ethoxycoumarin and ethoxyresorufin but had no effect on the 0-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[l,2-u: 3',2'-dlimidazole to mutagenic intermediates in the Ames test.3. Immunoquantification of two of the major families of cytochrome P-450, namely P450 I and P450 I1 B, using ELISA techniques showed that treatment with IQ induced the apoprotein levels of the P450 I family but4. 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 planar, molecule.The carcinogenicity of most chemicals is mediated, not by the parent form, but by reactive metabolic intermediates that readily interact with DNA initiating the process of tumourigenesis. By far the most prominent enzymes in the metabolic activation of chemical carcinogens are the ubiquitous monooxygenases whose terminal oxidase, cytochrome P-450, exists as a superfamily of proteins each of which confers to the system its characteristic substrate specificity [l].One of these families, namely P450 I (cytochromes P-448) appears to direct the metdbOhn of chemical carcinogens towards pathways that yield reactive species rather than inactive metabolites [2, 31. This family of isoenzymes is also involved in the activation of the aminoimidazo-azaarenes [4,5], which have been isolated from broiled fish and meat [6, 71. They are mutagens in a number of in vitro systems [8-111, activate a variety of oncogenes [12] and are potent animal carcinogens [I 3 -151. The prototype is IQ (2-amino-3-methylimidazo[4,5-flquinoline) whose activation proceeds through an initial N-hydroxylation to yield 2-amino-3-methyl-Nhydroxyimidazo[4,5-j~quinoline 1161, the proximate carcinogen, which undergoes further metabolism to generate the ultimate carcinogen [5]. The P450 I concentration in untreated animals is very small, immunologically calculated to be less than 5% of the total cytochrome P-450 content [17, 181, so that the activation of IQ is likely to be a minor pathway. However, many chemical carcinogens, such as the polycyclic The present study was therefore undertaken to establish if (a) IQ induces the rat hepatic monooxygenases, and (b) selectively induces the P450 I family that facilitates its activation. Since chemicals that inte...