Topical retinoic acid enhances, and a dark tan protects, from subedemal solar-simulated photocarcinogenesis

Studies into the effects of topical retinoic acid on photocarcinogenesis ha ve yielded ambiguous findings. This may be due to different Experimental pr otocols and ultraviolet spectra. Retinoic acid is commonly used for a range of dermatologic conditions, and therefore it is important to resolve wheth er it affects skin tumor formation. To address this issue we used a protoco l to mimic as closely as possible human use of retinoic acid. Two mouse str ains were used: Skh:HR-1 (albino) and Skh:HR-2 (lightly pigmented). The pig mented mice more closely resemble Caucasian skin as they develop a light ta n in response to ultraviolet radiation. This tan is greatly augmented by re tinoic acid. As these are congenic mice, any differences can be attributed to the development of a tan. Mice were exposed to solar-simulated ultraviol et radiation, followed by treatment with 0.05% retinoic acid. This modeled exposure to sunlight during the day followed by retinoic acid treatment and a night-time period in the absence of sunlight. As it is recommended that ultraviolet exposure is minimized when using topical retinoic acid, the mic e were only exposed to one-third of minimal edemal dose of ultraviolet radi ation per day. This retinoic acid protocol augmented photocarcinogenesis. R etinoic acid decreased the latency period, reduced the probability that a m ouse would survive without a tumor, and increased the number of tumors per mouse. All tumors induced were squamous cell carcinomas, and the skin betwe en the tumors on mice treated with retinoic acid was found to contain carci noma in situ upon histologic diagnosis. The light tan of the solvent-treate d pigmented mice did not provide any protection, whereas the dark tan, whic h developed in Skh:HR-2 mice in response to retinoic acid, reduced photocar cinogenesis but did not overcome the augmenting effect of retinoic acid. Th us, using this experimental design, topical retinoic acid augmented photoca rcinogenesis, and the ability to develop a dark but not light tan provided some, but limited, protection.