ULTRAVIOLET-IRRADIATION INDUCES C-FOS BUT NOT C-HA-RAS PROTOONCOGENE 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 exp osure, and c-Ha-ras mutations are commonly present in human skin neopl asms removed from chronically sun-exposed sites. In the present study, the effect of UV irradiation on the expression of these two proto-onc ogenes was examined. The sun-protected volar forearm of six subjects w as exposed to a standardized erythemogenic dose of solar-simulated lig ht, and punch biopsies were obtained after 1 h and 24 h from the irrad iated area and a nearby shielded area. Expression of c-fos, determined by in situ hybridization of histologic cross-sections, was detected i n 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 th e biopsy specimens. Our data demonstrate transient induction of c-fos but not c-Ha-ras expression, at least at the timepoints studied, follo wing 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 ski n and may facilitate the development of skin cancer.