EFFECT OF A CHEMICAL CARCINOGEN AND PHORBOL ESTERS ON STEROL-METABOLISM OF MOUSE SKIN

  • 1 January 1981
    • journal article
    • research article
    • Vol. 41  (7) , 2943-2949
Abstract
The effect of 20-methylcholanthrene [20-MC] and phorbol esters on sterol metabolism of mouse skin was studied. When 4.beta.-phorbol esters were administered to mice that were previously painted once with 20-MC, a depression of some sterols in skin occurred, of which that of lathosterol was most marked. This effect was not observed when the order of application was reversed. Using a metabolic inhibitor, diazacholesterol, it was shown that sterols which reduce in mouse skin by administration of carcinogen and promoters were similar to those which reduce by administration of carcinogen only and are the members of one of the 2 cholesterol-biosynthetic pathways, i.e., a pathway which proceeds through intermediates with a saturated side chain. The intensity of the lathosterol-depressing effect of phorbol esters depends on the order of application of 20-MC and promoters, the amount of promoters, molecular species of alcoholic moiety of esters and configuration at C-4 of phorbol moiety. 4.beta.-Phorbol-12-myristate-13-acetate revealed the highest activity, which was followed by 4.beta.-phorbol-12,13-didecanoate, 4.beta.-phorbol-12,13-dibutyrate, 4.beta.-phorbol-12,13-dibenzoate, 4.beta.-phorbol-12,13-diacetate, 4.alpha.-phorbol-12,13-didecanoate and 4.alpha.-phorbol. 4.alpha.-Phorbol was practically inactive. When .beta.-naphthoflavone was substituted for 20-MC, little effect was observed except in 4.beta.-phorbol-12-myristate-13-acetate, which revealed a rather marked lathosterol-depressing activity. Phorbol esters themselves did show some activity of lathosterol depression without prior application of 20-MC but the effects were much weaker. When anthralin was applied to mouse skin after the painting of 20-MC, a low but definite lathosterol-depressing effect was observed.