Benzo(a)pyrene (BaP), a major environmental pollutant and component of cigarette smoke, is both carcinogenic and atherogenic in experimental models. We investigated the effect of long-term administration of BaP on atherogenesis in both atherosclerosis-susceptible White Carneau (WC) and atherosclerosis-resistant Show Racer (SR) pigeons. The number and size of arterial lesions in the brachiocephalic arteries in WC and SR females but not males were significantly enhanced after long-term dosing

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... BaP. Metabolic activation appears to be required for BaP atherogenicity, since benzo(e)pyrene (BeP), a noncarcinogenic analogue of BaP, did not enhance lesion development. Studies with 3 H-BaP revealed no significant differences between male and female or between WC and SR pigeons in the arterial distribution of BaP and/or its metabolites. There were no consistent differences in blood pressure or plasma cholesterol levels between breeds or sexes. However, chronic administration of BaP did result in complete infertility in female birds, concomitant with grossly visible changes in ovarian appearance. These results clearly show that long-term dosing with BaP alters ovarian structure and function in treated birds, at the same time aggravating the development of arterial lesions. Thus, BaP-induced atherogenicity in female pigeons may be a consequence of an alteration in estrogen production or of antiestrogenic properties of BaP at the level of the arterial wall and may serve as a highly useful animal model to examine the well-known rapid development of atherosclerosis in postmenopausal women. (Arterioscler Thromb. 1993;13:1721-1727.) KEY WORDS • atherosclerosis • benzo(a)pyrene • pigeons • arterial change • females