Differences in H-2 recombinant mice in the beta-naphthoflavone inducibility of the mixed function monooxygenase, P1-450

Abstract

The influence of the major histocompatibility complex (H-2 in mouse) on induction of cytochrome P-450-dependent monooxygenase (P1-450) by the prototype polyaromatic hydrocarbon (PAH), beta-naphthoflavone, was investigated in C57BL/10 Sn (B10) recombinant congenic mice. The cytosolic Ah-receptor level, as measured by specific binding with [3H]-2,3,7,8-tetrachlorodibenzo-p-dioxin, was significantly lower in B10.A and B10.A(5R) than in either B10, B10.BR, or B10.A(2R), suggesting that the D region of H-2 influences Ah-receptor levels. The responsiveness to beta-naphthoflavone, as determined by increased catalytic activity toward benzo(a)pyrene and 7-ethoxycoumarin, was considerably lower in B10, B10.A, and B10.A(5R) than in B10.BR and somewhat lower than in B10.A(2R) or B10.A(4R) mice. The lower PAH responsiveness in B10.A and B10.A(5R) correlated with their lower Ah-receptor levels while that in B10 appeared to reflect a K-A region influence on PAH responsiveness that was not due to changed Ah-receptor levels. Thus, we conclude that more than one H-2 locus may influence PAH responsiveness, and by different mechanisms.