SPECIFIC INDUCTION OF HEPATIC CYTOCHROME P4501A-2 IN C57BL 6 AND DBA/2 MICE TREATED WITH 2-AMINO-3-METHYLIMIDAZO[4,5-F]QUINOLINE (IQ)/

The food mutagen/carcinogen 2-amino-3-methylimidazo[4,5-f]quinoline (I Q) is activated by cytochrome p4501a-2 via N-hydroxylation; various P4 50s may contribute to detoxification via ring hydroxylation. Alteratio ns in P450 levels by IQ treatment might therefore influence its toxici ty. To examine the role of Ah locus genotype on the biochemical effect s of IQ, C57BL/6 (Ah(b)Ah(b); p450Ia-1/2 inducible) and DBA/2 (Ah(d)Ah (d), noninducible) mice of both sexes were given IQ at varying doses, with different vehicles and routes of administration. Livers taken aft er 24 hours were assessed for total cytochrome p450 and activities of ethoxyresorufin-O-deethylase (EROD, a p4501a-1 activity, inducible in Ah(b) mice), methoxyresorufin-O-demethylase MROD, a p4501a-2 (activity ), and benzyloxyresorufin-O-dealkylase (BzROD, an activity of p4502b). There was little effect on total cytochrome p450, but all three enzym e activities were often induced, a maximum of 2.5-fold, in both sexes and in DBA/2 as well as C57BL/6 mice. However, Western immunoblot anal ysis with monoclonal antibodies demonstrated an increase only in p4501 a-2 protein. p4501a-1 remained undetectable. A monoclonal antibody to p4502-b recognized one protein band in liver microsomes from males and two bands in female mice of both strains. Amounts of these proteins w ere not altered by IQ treatment. Thus, IQ specifically, if moderately, induces its activating enzyme, p4501a-2, in a process that was not cl early related to Ah responsiveness.