title: Interactions of ultraviolet radiation, 12-O-tetradecanoyl-phorbol-13-acetate and retinoic acid in the skin of hairless mice.
abstract: Epidermal changes (mitosis, DNA synthesis, hyperplasia and acanthosis) were used to assay the effects of three different treatments on the dorsal skin of hairless mice: ultraviolet radiation (UVR), all-trans retinoic acid (RA) and/or 12-O-tetradecanoyl-phorbol-13-acetate (TPA). Mice receiving 20 exposures to fluorescent sunlamps in 4 wk (200 Robertson-Berger counts, or about one erythema dose daily, 5 days/wk) and subsequent topical application of methanol (3 applications/wk, beginning 3 wk after the end of UVR treatment) still displayed hyperproliferative cellular activity at least 17 wk after the final UV irradiation. Alone, either RA or TPA (0.001% in methanol, applied topically 3 times/wk) had similar hyperproliferative effects on the epidermis initially, but the skin appeared to adapt to continued treatment with TPA after 14 wk while RA-treated skin remained hyperproliferative. To study the effects of each reagent on UVR-exposed skin, an initiation-promotion protocol was used: repeated applications of the test compound were started 3 wk after the end of 4 wk of UVR exposures. By this method, treatment with either TPA or RA resulted in additional epidermal activity initially. However, although TPA-treated epidermis returned to the control level of activity by wk 21, no significant adaptation to RA treatment was seen.
mesh_terms: D000818:Animals; D002273:Carcinogens; D003043:Cocarcinogenesis; D004817:Epidermis / Q000187:drug effects / Q000473:pathology; D008297:Male; D051379:Mice; D008812:Mice, Hairless; D008938:Mitosis / Q000187:drug effects / Q000528:radiation effects; D009381:Neoplasms, Radiation-Induced / Q000209:etiology / Q000473:pathology; D010704:Phorbols / Q000633:toxicity*; D012878:Skin Neoplasms / Q000139:chemically induced / Q000209:etiology* / Q000473:pathology; D013755:Tetradecanoylphorbol Acetate / Q000633:toxicity*; D014212:Tretinoin / Q000633:toxicity*; D014466:Ultraviolet Rays / Q000009:adverse effects*
chemical_list: D002273:Carcinogens; D010704:Phorbols; D014212:Tretinoin; D013755:Tetradecanoylphorbol Acetate