Ultraviolet irradiation induces c-fos but not c-Ha-ras proto-oncogene expression in human epidermis

The link between sun exposure and skin cancer is well established, but the mechanism of photocarcinogenesis is still incompletely understood. In vitro experimentation has shown that induction of the c-fos proto-oncogene occurs in cultured human keratinocytes after ultraviolet exposure, and c-Ha-ras mutations are commonly present in human skin neoplasms removed from chronically sun-exposed sites. In the present study, the effect of UV irradiation on the expression of these two proto-oncogenes was examined. The sun-protected volar forearm of six subjects was exposed to a standardized erythemogenic dose of solar-simulated light, and punch biopsies were obtained after 1 h and 24 h from the irradiated area and a nearby shielded area. Expression of c-fos, determined by in situ hybridization of histologic cross-sections, was detected in the basal and lower epidermal layers in all biopsies. However, at 1 h there was a marked increase that returned to baseline by 24 h. c-Ha-ras mRNA could not be detected by riboprobe hybridization in any of the biopsy specimens. Our data demonstrate transient induction of c-fos but not c-Ha-ras expression, at least at the timepoints studied, following a modest UV exposure in normal skin. This phenomenon may lead to the subsequent constitutive over-expression and super-inducibility of c-fos observed in cultured keratinocytes derived from photodamaged skin and may facilitate the development of skin cancer.