Quantitative Assessment of Epidermal Melanogenesis in C3H/Tif hr/hr Mice Treated with Topical Furocoumarins and UVA Radiation

Abstract

We report quantitative data on epidermal melanogenesis by established and new furocoumarins. The ears and dorsal skin of pigmented hairless mice were treated for 12 d with compounds in ethanol, at equi-optical concentrations, and exposed to subphototoxic doses of ultraviolet A. Increased pigmentation was observed with 6,4,4'-trimethylangelicin > psoralen > 8-methoxypsoralen > 5-methoxypsoralen > 4,4',5'-trimethylazapsoralen = bergamot oil. Assessment of melanocyte numbers and morphology in epidermal sheet dihydroxyphenylalanine preparations showed that 6,4,4'-trimethylangelicin was the best compound with 536 ear melanocytes/mm2 +/- 15 SEM compared with 46 +/- 4 in controls. Psoralen induced 297/mm2 +/- 33, compared with its methoxy derivatives with ranges between 200 and 240/mm2.6,4,4'-trimethylangelicin had a striking effect on dorsal skin with 462 +/- 18 melanocytes/mm2 compared to less than 80/mm2 in all other ultraviolet A treatment groups. Khellin, 5-GOP and ultraviolet A only and all non-ultraviolet A controls had no effect. Melanogenesis was associated with increased dendricity, melanocyte size, especially with 5-methoxypsoralen, and giant melanocytes were noted with some treatments. The potency of 6,4,4'-trimethylangelicin, which does not form DNA interstrand crosslinks, may be related to its high DNA binding constant. Our data may be useful in the selection of compounds to treat vitiligo.