Roddey PK, Garmyn M, Park HY, Bhawan J, Gilchrest BA.
The Journal of investigative dermatology · 1994
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Abstract
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.