EFFECTS OF PROVITAMIN-A OR NON-PROVITAMIN-A CAROTENOIDS ON LIVER XENOBIOTIC-METABOLIZING ENZYMES IN MICE

To determine whether carotenoids can modulate xenobiotic-metabolizing enzymes in mice, catalytic activities of several phase I and phase II enzymes have been measured in liver microsomes and cytosol of male Swi ss mice fed diets containing beta-carotene, beta-apo-8'-carotenal, can thaxanthin, or astaxanthin (300 mg/kg diet) or treated with 3-methylch olanthrene (3-MC) (3 times at 50 mg/kg ip) for 15 days. Canthaxanthin increased CYP 1A-dependent activities: ethoxyresorufin O-deethylase (E ROD) was increased 3-fold, pentoxyresorufin dealkylase (PROD) was incr eased 2.5-fold, and methoxyresorufin O-demethylase (MROD) was increase d 1.6-fold; these increases were much less than those induced by 3-MC, which induced EROD 49-fold, PROD 10-fold, and MROD 4-fold. 3-MC, but not canthaxanthin, also increased relative liver weight, liver P-450 c ontent, NADH-cytochrome c reductase, and benzoxyresorufin dearylase. T he three other carotenoids had little or no effect on phase I enzymes. Among the phase II enzyme activities, only NADPH-quinone reductase wa s slightly increased by 3-MC and carotenoids, except beta-carotene. Am ong the three carotenoids that have previously been found to be powerf ul CYP 1A inducers in the rat, i.e., canthaxanthin, astaxanthin, and b eta-apo-8'-carotenal, only canthaxanthin shows some (weak) inducing ef fect of CYP 1A in the 3-MC-responsive Swiss mice, indicating that the mechanism of CYP 1A induction by carotenoids may not be the same as th at by 3-MC. In addition, the fact that beta-carotene has no effect on the tested enzymes does not support the hypothesis that the modulation of xenobiotic metabolism is a possible mechanism for the antimutageni c and anticarcinogenic effects of beta-carotene, which have been demon strated in several in vivo models in mice.