Effects of palm carotenoids in rat hepatic cytochrome P450-mediated benzo(a)pyrene metabolism

Abstract

Using benzo(a)pyrene (BaP) metabolism as a probe for chemical carcinogenesis, in vitro and in vivo effects of palm-oil carotenoid [β-carotene (BC), α-carotene (AC), or canthaxanthin (CTX)] on BaP metabolism in the rat hepatic cytochrome P₄₅₀-mediated monooxygenase system were studied. Apparent Michaelis-Menten constants (K_m) for formation of the precursor carcinogen, 7,8-dihydrodiol BaP, were found to be 14.4 (BC), 1.74 (AC), and 0.7 (CTX) µmol/L. The order of anticarcinogenic strength established in this study was BC ≫ AC > CTX. Increased formation of the detoxification intermediate, 3-hydroxy BaP, with increased carotenoid concentration was observed. The order of detoxification strength was BC > AC = CTX. The presence of carotenoids in vivo inhibited BaP metabolism. Using 9,10-dihydrodiol BaP as an indicator for inhibition, the order of the antioxidative activity was palm oil (with carotenoids) > BC > CTX > palm oil (without carotenoids). BC and AC may selectively modify the rat-liver microsomal enzymes, thus providing a biochemical mechanism for the inhibitory effect of palm carotenoids on chemical carcinogenesis.