BETA-APO-8'-CAROTENAL, BUT NOT BETA-CAROTENE, IS A STRONG INDUCER OF LIVER CYTOCHROMES P4501A1 AND 1A2 IN RAT

1. The catalytic activities of several phase I and II xenobiotic-metab olizing enzymes and their immunochemical detection have been investiga ted in liver microsomes and cytosol of the male rat, which had been fe d for 15 days with diets containing 300 mg/kg beta-carotene isomers (a ll-trans beta-carotene or beta-carotene from Dunaliella salina rich in 9-cis isomer or isomerized beta-carotene), or apocarotenoids as beta- apo-8'-carotenal, ethyl beta-apo-8'-carotenoate and citranaxanthin. 2. beta-carotene, either all-trans or containing cis isomers, did not in duce any significant change in the measured activities. By contrast, b eta-apo-8'-carotenal increased the liver content of cytochrome P450, t he activity of NADH- and NADPH-cytochrome c reductase, and strongly in creased some cytochrome P450-dependent activities, particularly ethoxy resorufin O-deethylase (x 158), methoxyresorufin O-demethylase (x 22), pentoxy- and benzoxyresorufin O-dealkylases, but did not affect eryth romycin N-demethylase nor nitrosodimethylamine N-demethylase activitie s. Phase II p-nitrophenol- and 4-hydroxybiphenyl-uridine diphosphogluc uronosyl transferase activities were also increased by beta-apo-8'-car otenal. Western blots of microsomal proteins clearly showed the induct ion of CYP1A1 and 1A2 by beta-apo-8'-carotenal. This induction profile resembles that produced by two other carotenoids: canthaxanthin and a staxanthin. Ethyl beta-apo-8'-carotenoate and citranaxanthin showed si milar effects to beta-apo-8'-carotenal but of less intensity. 3. Three carotenoids: beta-apo-8'-carotenal, canthaxanthin and astaxanthin, ar e inducers of CYP1A1 and 1A2 in the rat. These carotenoids form a new class of inducers of CYP1A, structurally very different from the class ical inducers as 3-methylcholanthrene, beta-naphtoflavone or dioxin.