Modulation of c-jun and c-fos Transcription by UVB and UVA Radiations in Human Dermal Fibroblasts and KB Cells

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Abstract
We have previously demonstrated that the oxidizing component of ultraviolet‐A (UVA) plays a central role in the activation of the nuclear oncogene and transcription factor, c‐fos, in cultured human skin fibroblasts. We have now shown that expression of both c‐jun and c‐fos (AP‐1) family of transcription factors is modulated by short and long wavelength solar ultraviolet (UV) radiation in human fibroblasts and human KB cells. UVA radiation activated c‐jun and c‐fos in both fibroblasts and KB cells, whereas ultraviolet‐B (UVB) radiation activates such oncogenes only in KB cells. Moreover, decreasing the intracellular levels of reducing equivalents in human fibroblasts by glutathione (GSH) depletion lowered the UVA dose threshold for c‐jun and c‐fos activation several‐fold and greatly amplified the UVA‐mediated activation of such genes. A more modest effect was observed in GSH‐depleted KB cells. In both GSH‐depleted fibroblasts and KB cells, UVB radiation failed to amplify c‐jun and c‐fos activation indicating that the oxidative component of UVB plays a minor role in the modulation of such oncogene expression. These findings clearly indicate that both c‐jun and c‐fos are activated by the oxidizing component of UVA radiation in human fibroblasts and KB cells, while UVB‐mediated modulation seems to be restricted to human epithelial cells and does not involve oxidizing intermediates.