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American Journal of Pathology, Vol 148, 1113-1123, Copyright © 1996 by American Society for Investigative Pathology

REGULAR ARTICLES

Decreased DNA repair but normal apoptosis in ultraviolet-irradiated skin of p53-transgenic mice

G Li, DL Mitchell, VC Ho, JC Reed and VA Tron
Department of Medicine, Vancouver Hospital and Health Science Centre, British Columbia, Canada.

p53 tumor suppressor plays a vital role in the cellular responses to genotoxic stress. It is believed that p53 regulates the cell cycle by activating the G1 checkpoint after exposure to agents like ionizing radiation, ultraviolet (UV) radiation, or genotoxic chemicals. Recently, it is conjectured that p53 may have additional functions in DNA repair and apoptosis. Previously, we demonstrated that p53- transgenic mice that carry mutant alleles of a p53 gene developed twice as many skin tumors as control mice after UV exposure. To elucidate the molecular mechanisms of mutant p53 in skin cancers, we studied DNA repair efficiency and the rate of apoptosis in murine keratinocytes after UV irradiation. In this report, we show that mutant p53- transgenic mouse skin has reduced repair of UV-induced DNA damage in both in vivo and in vitro radioimmunoassays. In control mice, DNA repair is associated with increased amounts of wild-type P53 protein. Unexpectedly, mutant p53-transgenic mice had slightly increased apoptosis after UV irradiation, suggesting that the wild-type p53 protein in the cells still functions in inducing apoptosis, or that this cell death results from p53-independent mechanisms. These results suggest that mutant p53 interferes with wild-type p53 in the repair of UV-induced DNA damage but not in apoptosis.

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