Active oxygen species mediate the solar ultraviolet radiation-dependent increase in the tumour suppressor protein p53 in human skin fibroblasts.
Active oxygen species mediate many of the biological consequences of exposing cultured human skin cells to solar ultraviolet (UV) radiation (290-380 nm). A critical step in the escape from the carcinogenic potential of UV radiation is mediated by the protein p53. P53 activates growth arrest, allowing for DNA repair, and apoptosis, which removes damaged 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 radiation increased p53, and agents that scavenge active oxygen species, N-acetylcysteine, ascorbate and alpha-tocopherol, inhibited the increase. The generation of DNA single strand breaks has been proposed to be an important step in the pathway leading to the increase in p53 initiated by a variety of cytotoxic agents. In this study I show that compounds that allow the accumulation of DNA single strand breaks, ara c and 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 radiation-dependent increase in p53, the increase caused by solar UV radiation occurs by an alternative mechanism involving active oxygen species.
Vile
G F
GF
Department of Pathology, Christchurch School of Medicine, New Zealand. gvile@chmeds.ac.nz
D000111:Acetylcysteine / Q000494:pharmacology; D001205:Ascorbic Acid / Q000494:pharmacology; D002478:Cells, Cultured; D004249:DNA Damage; D005347:Fibroblasts; D016166:Free Radical Scavengers / Q000494:pharmacology; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D007700:Kinetics; D017382:Reactive Oxygen Species / Q000378:metabolism*; D012867:Skin / Q000378:metabolism*; D013472:Sunlight; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D014466:Ultraviolet Rays; D014810:Vitamin E / Q000494:pharmacology
D016166:Free Radical Scavengers; D017382:Reactive Oxygen Species; D016159:Tumor Suppressor Protein p53; D014810:Vitamin E; D006861:Hydrogen Peroxide; D001205:Ascorbic Acid; D000111:Acetylcysteine