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.