Effects of ultraviolet C radiation on cellular proliferation in p53-/- keratinocytes

Skin cancer is the most common tumor type in Caucasians, with an incidence that approaches the lifetime risk for all other cancer subtypes combined. The most common predisposing factor is exposure to ultraviolet (UV) radiation present in sunlight. The purpose of this investigation was to evaluate the effects of UVC on the proliferation of a p53-/- human keratinocyte cell line, HaCaT, and how UVC alters the response of these cells to transforming growth factors (TGF)-alpha and TGF-beta1. UVC treatment during G0/G1 phase resulted in decreased incorporation of [3H]thymidine, an effect that was enhanced by pretreatment with TGF-beta1. However, irradiation of HaCaT cells in S or G2/M phase had no effect on the incorporation of [3H]thymidine, suggesting that these cells failed to undergo G2/M arrest in response to UV-mediated DNA damage. UVC had no effect on TGF-beta1-mediated growth inhibition, but decreased the mitogenic response of HaCaT cells to TGF-alpha. Seven days after irradiation, there were no differences between the number of cells that were exposed to UVC and those that were not, suggesting that the effects of UVC on proliferation of HaCaT cells was transient. These results suggested that UVC did not stimulate proliferation of p53-/- HaCaT cells, or cause cell cycle arrest in G2/M, which would allow transmission of chromosomal damage to daughter cells during M phase. Failure of the G2/M cell cycle checkpoint may be one of the mechanisms by which p53 results in genomic instability.