Inhibition of phorbol ester--induced human epidermal ornithine decarboxylase activity by oral compounds: a possible role in human chemoprevention studies.
Extensive animal data have suggested that, in some systems, the induction of ornithine decarboxylase (ODC) is an essential, although not sufficient, aspect of tumor promotion and that compounds that inhibit ODC can inhibit tumor formation. Using fasting human volunteers, we report that human epidermal and dermal ODC are consistently induced by the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) in a manner similar to that seen in mouse skin. There is a marked intersubject variation in TPA-induced epidermal ODC activity levels. Orally administered compounds significantly inhibited TPA-caused human epidermal ODC induction. These data may be useful in the further development of drugs, doses, and dose schedules for use in human cancer chemoprevention studies.
D000328:Adult; D002478:Cells, Cultured; D004790:Enzyme Induction / Q000187:drug effects; D005260:Female; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology*; D015474:Isotretinoin; D008297:Male; D065108:Ornithine Decarboxylase Inhibitors; D012867:Skin / Q000187:drug effects* / Q000201:enzymology; D012878:Skin Neoplasms / Q000139:chemically induced / Q000517:prevention & control; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014212:Tretinoin / Q000494:pharmacology*
D065108:Ornithine Decarboxylase Inhibitors; D014212:Tretinoin; D015474:Isotretinoin; D013755:Tetradecanoylphorbol Acetate; D007213:Indomethacin