Ultraviolet B-radiation dose influences the induction of apoptosis and p53 in human keratinocytes.
p53 is a tumor suppressor gene that has been implicated in a number of important cellular processes, including DNA repair and apoptosis. Genomic damage in human keratinocytes caused by ultraviolet B (UVB) irradiation has been shown to induce both apoptosis and p53 expression. We have previously observed that p53 expression in cultured normal human keratinocytes is predominantly perinuclear; however, exposure of cells to UVB radiation induces a major shift of p53 expression to the nucleus. Using terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end-labeling, internucleosomal DNA ladders and flow cytometry, we correlated observed changes in p53 expression with the induction of apoptosis at low, intermediate and high doses of UVB radiation. High doses of UVB radiation induced cells to undergo apoptosis, whereas UVB radiation at low doses did not induce apoptosis but appeared to stimulate repair of the DNA damage induced by UVB radiation. Intermediate doses of UVB radiation induced a heterogeneous population of cells to undergo either DNA repair or apoptosis. The level of UVB radiation dose also influenced the induced cellular localization of p53. These observed differences in p53 cellular localization correlated with the induction of DNA repair or apoptosis. In cells undergoing apoptosis, p53 protein was found within the blebs of the degenerating nuclei. Our data give support to increasing evidence that p53 may play a role in both the repair of UV-radiation-induced DNA damage and the induction of apoptosis, and may function as a central control checkpoint in response to UVB-radiation-induced DNA damage.
Cotton
J
J
Department of Dermatology, Indiana University School of Medicine, Indianapolis 46202, USA.
Spandau
D F
DF
D017209:Apoptosis / Q000528:radiation effects*; D002478:Cells, Cultured; D004249:DNA Damage; D053938:DNA Fragmentation; D004307:Dose-Response Relationship, Radiation; D005434:Flow Cytometry; D005786:Gene Expression Regulation / Q000528:radiation effects*; D016158:Genes, p53; D006801:Humans; D015603:Keratinocytes / Q000166:cytology / Q000378:metabolism / Q000528:radiation effects*; D008297:Male; D008856:Microscopy, Fluorescence; D013347:Subcellular Fractions / Q000737:chemistry; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis*; D014466:Ultraviolet Rays
D016159:Tumor Suppressor Protein p53