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.
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