ACTIVE OXYGEN SPECIES MEDIATE THE SOLAR ULTRAVIOLET RADIATION-DEPENDENT INCREASE IN THE TUMOR-SUPPRESSOR PROTEIN P53 IN HUMAN SKIN FIBROBLASTS

Active oxygen species mediate many of the biological consequences of e xposing cultured human skin cells to solar ultraviolet (UV) radiation (290-380 nm). A critical step in the escape from the carcinogenic pote ntial of UV radiation is mediated by the protein p53. P53 activates gr owth arrest, allowing for DNA repair, and apoptosis, which removes dam aged cells. Here I show that p53 in cultured human skin fibroblasts is elevated after treatment with hydrogen peroxide, an oxidant produced in cells during exposure to solar UV radiation. Simulated solar UV rad iation increased p53, and agents that scavenge active oxygen species, N-acetylcysteine, ascorbate and alpha-tocopherol, inhibited the increa se. The generation of DNA single strand breaks has been proposed to be an important step in the pathway leading to the increase in p53 initi ated by a variety of cytotoxic agents. In this study I show that compo unds that allow the accumulation of DNA single strand breaks, ara c an d hydroxyurea, enhanced the UVC radiation (254 nm)-dependent increase in p53, but had no effect on the solar UV radiation-dependent increase . Thus, while DNA single strand breaks are involved in the UVC radiati on-dependent increase in p53, the increase caused by solar UV radiatio n occurs by an alternative mechanism involving active oxygen species. (C) 1997 Federation of European Biochemical Societies.