INHIBITION OF SKIN TUMOR PROMOTION BY RETINOIC ACID AND ITS METABOLITE 5,6-EPOXYRETINOIC ACID

  • 1 January 1980
    • journal article
    • research article
    • Vol. 40  (7) , 2367-2371
Abstract
The ability of 5,6-epoxyretinoic acid, a biologically active metabolite of retinoic acid, to inhibit the induction of ornithine decarboxylase (ODC) activity and skin tumor promotion by 12-O-tetradecanoylphorbol-13-acetate (TPA) was evaluated. Application of 5,6-epoxyretinoic acid concurrently with or 1 h after each application of TPA to the initiated mouse skin inhibited the formation of skin tumors as effectively as did retinoic acid. 5,6-Dihydroretinoic acid, which is a poor substrate for epoxidation, also inhibited skin tumor promotion. 5,6-Epoxyretinoic acid, 5,6-dihydroretinoic acid and retinoic acid were equally effective in inhibiting the induction of ODC activity by TPA. Insect juvenile hormones inhibited neither the induction of ODC activity nor skin tumor promotion by TPA. Epoxidation of retinoic acid at the 5,6-position is apparently not a rate-limiting modification for the antipromoting activity of retinoic acid. Inhibition of the induction by TPA of mouse epidermal ODC activity may be a simple test for screening the potential prophylactic activities of new retinoids.