Topical all-trans retinoic acid augments ultraviolet radiation-induced increases in activated melanocyte numbers in mice

We have previously shown that daily application of 0.05% retinoic acid to t he backs of lightly pigmented, hairless HRA:Skh-2 mice increases melanogene sis resulting from exposure to solar-simulated ultraviolet radiation. In th is study we show that as early as 1 wk following commencement of treatment, there is a 2-fold increase in the number of epidermal 3,4-dihydroxyphenyla lanine positive melanocytes in retinoic acid and ultraviolet radiation trea ted HRA:Skh-2 mice compared with mice that received ultraviolet radiation o nly. This increased to a 2.9-fold difference by 6 wk. Retinoic acid also au gmented ultraviolet radiation-stimulated melanogenesis, with a 4-fold incre ase being observed after only 2 wk. These findings were also seen in C57BL mice. Ultraviolet radiation and retinoic acid needed to be applied to the s ame skin site for the augmentation in melanocyte activation to occur. Ultra violet B rather than ultraviolet A was mainly responsible for melanogenesis and the retinoic acid primarily increased ultraviolet B-induced melanogene sis. Furthermore, retinoic acid on it's own, in the absence of ultraviolet radiation caused a small but statistically significant increase in 3,4-dihy droxyphenylalanine positive melanocyte numbers and melanogenesis. Thus topi cal retinoic acid is a potent modulator of melanocyte activation. Alone it is able to increase the number of activated epidermal melanocytes and make melanocytes more sensitive to activation by ultraviolet B.