Oxidative stress is involved in the UV activation of p53.
In many vertebrate cells exposure to ultraviolet light lead to a dramatic increase in the cellular levels of the tumour suppressor protein p53, followed by a biological response of either growth arrest or programmed cell death. Ultraviolet light can be absorbed directly by cellular macromolecules, leading to photochemical modification of DNA and proteins. Additionally, it also causes free radical formation, resulting in oxidative stress. Whereas ultraviolet light and ionizing radiation both induce DNA lesions which trigger an activation of the p53 pathway, the magnitude of the p53 response elicited by ionizing radiation is comparatively low. Following irradiation with ultraviolet light two populations of p53-reactive cells are induced: a population accumulating high levels of p53 protein and a population with comparatively low levels of p53, similar in magnitude to the p53 response following ionizing radiation. Pretreatment of cells with N-acetylcysteine, an agent known to counteract oxidative stress, attenuates the cellular p53 response to ultraviolet light by reducing the number of cells with high p53 levels but does not affect the response to ionizing radiation. We demonstrate that N-acetylcysteine pretreatment does not prevent the inflicted DNA damage and therefore conclude that oxidative stress is a causative agent in the ultraviolet light activation of the p53 pathway.
Renzing
J
J
Department of Biochemistry, University of Dundee, UK.
Hansen
S
S
Lane
D P
DP
D016475:3T3 Cells; D000111:Acetylcysteine / Q000494:pharmacology; D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D004249:DNA Damage / Q000187:drug effects / Q000528:radiation effects; D005347:Fibroblasts / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D016193:G1 Phase / Q000187:drug effects / Q000528:radiation effects; D051379:Mice; D008969:Molecular Sequence Data; D018384:Oxidative Stress / Q000502:physiology*; D011836:Radiation Tolerance; D016159:Tumor Suppressor Protein p53 / Q000187:drug effects / Q000528:radiation effects*; D014466:Ultraviolet Rays
D016159:Tumor Suppressor Protein p53; D000111:Acetylcysteine