AH RECEPTOR-DEPENDENT CYP1A INDUCTION BY 2 CAROTENOIDS, CANTHAXANTHINAND BETA-APO-8'-CAROTENAL, WITH NO AFFINITY FOR THE TCDD BINDING-SITE

The assays of several phase I and phase II xenobiotic-metabolizing enz yme activities, as well as CYP1A immunoblot analysis, were performed i n liver microsomes and cytosol of male C57BL/6 mice (Ah receptor-respo nsive), of male DBA/2 mice (Ah receptor-low responsive) and of female Ah receptor gene knockout mice that were fed diets containing 300 mg/k g of a nonprovitamin A carotenoid, canthaxanthin, or a provitamin A ca rotenoid, beta-apo-8'-carotenal for 14 days, or which were injected i. p. with 3-methylcholanthrene. Previous studies have shown that some ca rotenoids, such as canehaxanthin and beta-apo-8'-carotenal, are strong inducers of liver CYP1A1 and 1A2 when given to rats. In this work, on ly canthaxanthin induced both CYP1A1 and 1A2 in C57BL/6 mice, whereas beta-apo-8'-carotenal induced only CYP1A2 in this strain. Neither of t he two carotenoids modified CYP1A1/2 protein contents or enzyme activi ties in Ah receptor-low responsive DBA/2. or in Ah receptor gene knock out mice. Cytosol prepared from C57BL/6 mice liver tissue was incubate d with [H-3] 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in the presenc e of canthaxanthin or beta-apo-8'-carotenal and analyzed by sucrose de nsity gradient sedimentation: neither of the carotenoids, even when pr esent in large excess, competed with TCDD for the TCDD binding site of the cytosolic Ah receptor of C57BL/6 mice. In brief, the carotenoids canthaxanthin or beta-apo-8'-carotenal induced Cypla genes in mice thr ough an Ah receptor-dependent pathway, but did not bind to the Ah rece ptor. (C) 1997 Elsevier Science Inc.