Carcinogenesis and atherogenesis: differences in monooxygenase inducibility and bioactivation of benzo[a]pyrene in aortic and hepatic tissues of atherosclerosis-susceptible versus resistant pigeons.

Atherosclerosis-susceptible White Carneau (WC-2) pigeons were compared with atherosclerosis-resistant Show Racer (SR-39) pigeons in terms of hepatic and aortic biotransformation and bioactivation of benzo[a]pyrene (B[a]P). Following pretreatment of the two strains with 3-methylcholanthrene (MC, 40 mg/kg), WC-2 hepatic 9000 X g supernatant fractions (S-9) exhibited consistently greater increases in the production of specific B[a]P metabolites when compared with uninduced controls than did the corresponding SR-39 preparations. Analyses of organic solvent-extractable metabolites with h.p.l.c. revealed that inducer pretreatment resulted in significantly greater increases (18- versus 7-fold) in the generation of B[a]P-7,8-dihydrodiol by WC-2 versus SR-39 hepatic S-9. Similar differences in inducibility were found for most other metabolites appearing in the h.p.l.c. profiles. Hepatic monooxygenase systems were induced in both strains following treatment of pigeons with a mixture of polychlorinated biphenyls (Aroclor 1254, 500 mg/kg); WC-2 birds again demonstrated greater responsiveness. Bioactivation of B[a]P to mutagenic (but not cytotoxic) products by hepatic S-9 was more effective in preparations from MC-pretreated WC-2 versus SR-39 pigeons when assessed with Salmonella typhimurium tester strains. Aortic homogenates from MC-pretreated pigeons displayed even greater inducibility differences than were observed with hepatic preparations. Inducer-mediated increases in the formation of B[a]P-7,8- and B[a]P-9,10-dihydrodiols were approximately 10- and 12-fold greater in WC-2 than SR-39 aortic preparations, respectively. The results document marked differences in biotransformation and bioactivation of carcinogenic hydrocarbons by atherosclerosis-susceptible and resistant pigeons and are reminiscent of the metabolic differences observed in carcinogenesis-susceptible and resistant strains of mice. It is suggested that these pigeon strains might offer a promising system in which to further study the role of target tissue biotransformation in the atherogenic actions of polynuclear aromatic hydrocarbons.