Differentiation of cultured epidermal keratinocytes related to sterol metabolism and its retardation by chemical carcinogens.
The amount of 5 beta-cholest-7-en-3 beta-ol of mouse dorsal skin was increased after parturition until 10 days of age, reaching a maximum 5 beta-cholest-7-en-3 beta-ol/5-cholesten-3 beta-ol ratio of 0.43. [2-14C]Acetate was incorporated almost exclusively into 5-cholesten-3 beta-ol in the basal cell culture of epidermal keratinocytes. However, when the concentration of calcium was changed from 0.07 to 1.9 mM to induce terminal differentiation of keratinocytes, a definite amount of radioactive acetate was incorporated into 5 beta-cholest-7-en-3 beta-ol. The extent of the incorporation was increased at least until 72 h after changing medium, and the ratio of radioactive 5 beta-cholest-7-en-3 beta-ol/radioactive 5-cholesten-3 beta-ol was constantly increased in this period, indicating that the accumulation of 5 beta-cholest-7-en-3 beta-ol in the cell is concomitant with the differentiation of the cell. Pretreatment with chemical carcinogens such as 7,12-dimethylbenz[a]anthracene and 20-methylcholanthrene inhibited the incorporation of radioactive acetate into 5 beta-cholest-7-en-3 beta-ol in the high calcium medium at least for the initial 24 h. After that, the incorporation was gradually restored to the normal level. Pretreatment with a tumor promoter, such as 12-O-tetradecanoyl-phorbol 13-acetate, however, did not inhibit the incorporation. Thus, sterol metabolism is suggested to be a useful indicator for differentiation of epidermal keratinocytes.
D015127:9,10-Dimethyl-1,2-benzanthracene / Q000494:pharmacology; D000085:Acetates / Q000378:metabolism; D019342:Acetic Acid; D000375:Aging; D000818:Animals; D002273:Carcinogens / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects; D002784:Cholesterol / Q000378:metabolism; D000078404:Epidermal Cells; D004817:Epidermis / Q000378:metabolism; D007633:Keratins / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D013261:Sterols / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D000085:Acetates; D002273:Carcinogens; D013261:Sterols; D015127:9,10-Dimethyl-1,2-benzanthracene; D007633:Keratins; C001521:lathosterol; D002784:Cholesterol; D013755:Tetradecanoylphorbol Acetate; D019342:Acetic Acid