Stimulatory effect of 1 alpha, 25-dihydroxyvitamin D3 on the formation of skin tumors in mice treated chronically with 7,12-dimethylbenz[a]anthracene.
The effect of 1 alpha, 25-dihydroxyvitamin D3 (1 alpha, 25-(OH)2D3) and its 24,24-difluoro analog on the formation of skin tumors in mice was evaluated in a complete carcinogenesis model using 7,12-dimethylbenz[a]anthracene (DMBA) as the carcinogen. Twice weekly topical application of 0.25-0.50 nmol of 1 alpha, 25-(OH)2D3 or 0.05-0.10 nmol of the difluoro analog of 1 alpha, 25-(OH)2D3 1 hour prior to treatment with 50 nmol DMBA stimulated tumor formation several fold compared to animals receiving DMBA alone. Topical application of 0.50 nmol of 1 alpha, 25-(OH)2D3 24 hours after treatment with DMBA, or half of this dose of the vitamin D3 metabolite, applied 1 hour before and 24 hours after treatment with DMBA, also stimulated tumor formation several fold. These results are in marked contrast to the potent inhibitory effect of 1 alpha, 25-(OH)2D3 and its difluoro analog on the formation of skin tumors in mice promoted by 12-O-tetradecanoylphorbol-13-acetate.
D015127:9,10-Dimethyl-1,2-benzanthracene; D000096:Acetone / Q000494:pharmacology; D000818:Animals; D001835:Body Weight; D002117:Calcitriol / Q000031:analogs & derivatives / Q000494:pharmacology; D003043:Cocarcinogenesis; D005260:Female; D051379:Mice; D012878:Skin Neoplasms / Q000139:chemically induced*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013997:Time Factors; D014212:Tretinoin / Q000494:pharmacology
D000096:Acetone; D014212:Tretinoin; D015127:9,10-Dimethyl-1,2-benzanthracene; C023370:24,24-difluoro-1,25-dihydroxyvitamin D3; D002117:Calcitriol; D013755:Tetradecanoylphorbol Acetate