Suppression of UVB-induced c-fos and c-jun expression in human keratinocytes by N-acetylcysteine.

Irradiation of human keratinocytes with UVB results in the early induction of proto-oncogenes c-fos and c-jun, members of the AP-1 protein family of transcription factors. To explore a possible involvement of oxidant stress in triggering this UVB-induced early gene response, we investigated in human keratinocytes the effect of N-acetylcysteine (NAC), a thiocompound with antioxidant activities, on UVB-induced c-fos, and c-jun expression. Normal human keratinocytes were irradiated with either 16 or 32 mJ cm-2 UVB, which induces a temporary inhibition of DNA synthesis, without compromising cell survival. Preincubation with 1 and 3 mM NAC suppressed c-jun and c-fos induction by UVB in a dose-dependent fashion. These applied concentrations of NAC were not toxic to the keratinocytes, as determined by Trypan Blue exclusion assay and completely suppressed c-jun and c-fos induction by the chemical cadmium chloride (oxidative stress). These results indicate that oxidative stress, at least in part, mediates the transcriptional activation of c-fos and c-jun in human keratinocytes after UVB irradiation.