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Sunburn and p53 in the onset of skin cancer


SQUAMOUS cell carcinoma of the skin (SCC) can progress by stages: sun-damaged epidermis, with individual disordered keratin-ocytes; actinic keratosis (AK), spontaneously regressing keratin-ized patches having aberrant cell differentiation and proliferation; carcinoma in situ; SCC and metastasis1–3. To understand how sunlight acts as a carcinogen, we determined the stage at which sunlight mutates the p53 tumour-suppressor gene and identified a function for p53 in skin. The p53 mutations induced by ultraviolet radiation and found in >90% of human SCCs4,5 were present in AKs. Inactivating p53 in mouse skin reduced the appearance of sunburn cells6, apoptotic keratinocytes generated by overexposure to ultraviolet. Skin thus appears to possess a p53-dependent 'guardian-of-the-tissue' response to DNA damage which aborts precancerous cells. If this response is reduced in a single cell by a prior p53 mutation, sunburn can select for clonal expansion of the p53-mutated cell into the AK. Sunlight can act twice: as tumour initiator and tumour promoter.

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Ziegler, A., Jonason, A., Leffellt, D. et al. Sunburn and p53 in the onset of skin cancer. Nature 372, 773–776 (1994).

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