Although tretinoin in itself is not tumorigenic, it has been shown that, under certain conditions, topical tretinoin can enhance the carcinogenic effect of UV radiation in Skh-1 hairless albino mice. This mouse species is a nocturnal rodent that lacks melanin, has a thin skin and may have a compromised DNA repair mechanism. A total of 12 studies, which were of different designs, have been performed. The light sourve, UV dose and duration of exposure, vehicle, tretinoin concentrations, treatment regimens and animal strains that were used varied, so it is difficult to draw any overall conclusion. In six of these studies there was enhanced UVB-induced turmorigeniciy, whereas in three studies there was inhibition of tumour formation, and in three there was no effect.
An important consideration is the control groups in these UV irradiation studies. Mice that had not been exposed to UV radiation, but were treated with topical tretinoin for 55 weeks, did not develop cutaneous toxicity or tumours. This course of treatment, which has been calculated to be equivalent to 35 years of constant application of tretinoin in humans, did not provide evidence of any clinically sigificant side effects other than the histological finding of epidermal hyperplasia, which is a typical retinoid effect.
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