TY - JOUR
T1 - Sunlight and sunburn in human skin cancer
T2 - P53, apoptosis, and tumor promotion
AU - Brash, Douglas E.
AU - Ziegler, Annemarie
AU - Jonason, Alan S.
AU - Simon, Jeffrey A.
AU - Kunala, Subrahmanyam
AU - Leffell, David J.
PY - 1996
Y1 - 1996
N2 - Sunlight is a carcinogen to which everyone is exposed. Epidemiology indicates that most carcinogenic sunlight exposure takes place several decades before the tumor arises. Some of the early events have been identified by searching for genes having ultraviolet (UV)-specific mutations. Over 90% of squamous cell carcinomas and more than 50% of basal cell carcinomas from New England patients contain UV-like mutations in the p53 tumor suppressor gene. From the mutation pattern, it can be concluded that the carcinogenic DNA lesions were pyrimidine-cytosine photoproducts caused by the UVB portion of sunlight. Particular codons of the p53 gene are most susceptible, apparently because of slower DNA repair at specific sites. Sunlight is sufficiently mutagenic often to mutate both p53 alleles. These mutations are also found in the precancer for squa-mous cell carcinoma, actinic keratosis, implying an early role. The function of p53 in normal skin is indicated by the observation that inactivating p53 in mouse skin reduces the appearance of sunburn cells, apoptotic keratinocytes generated by UV overexposure. Skin thus appears to possess a p53-dependent "cellular proofreading" response to DNA damage in which precancerous cells self-destruct. If this response is reduced in a single cell by a prior p53 mutation, sunburn can thereafter select for clonal expansion of the p53-mutated cell into an actinic keratosis. Sunlight appears to act twice: as tumor initiator and as tumor promoter.
AB - Sunlight is a carcinogen to which everyone is exposed. Epidemiology indicates that most carcinogenic sunlight exposure takes place several decades before the tumor arises. Some of the early events have been identified by searching for genes having ultraviolet (UV)-specific mutations. Over 90% of squamous cell carcinomas and more than 50% of basal cell carcinomas from New England patients contain UV-like mutations in the p53 tumor suppressor gene. From the mutation pattern, it can be concluded that the carcinogenic DNA lesions were pyrimidine-cytosine photoproducts caused by the UVB portion of sunlight. Particular codons of the p53 gene are most susceptible, apparently because of slower DNA repair at specific sites. Sunlight is sufficiently mutagenic often to mutate both p53 alleles. These mutations are also found in the precancer for squa-mous cell carcinoma, actinic keratosis, implying an early role. The function of p53 in normal skin is indicated by the observation that inactivating p53 in mouse skin reduces the appearance of sunburn cells, apoptotic keratinocytes generated by UV overexposure. Skin thus appears to possess a p53-dependent "cellular proofreading" response to DNA damage in which precancerous cells self-destruct. If this response is reduced in a single cell by a prior p53 mutation, sunburn can thereafter select for clonal expansion of the p53-mutated cell into an actinic keratosis. Sunlight appears to act twice: as tumor initiator and as tumor promoter.
KW - Mutagenesis
KW - Sunburn cells
KW - Ultravioletl actinic keratosis
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M3 - Article
C2 - 9627707
AN - SCOPUS:0030112303
SN - 1087-0024
VL - 1
SP - 136
EP - 142
JO - The journal of investigative dermatology. Symposium proceedings / the Society for Investigative Dermatology, Inc. [and] European Society for Dermatological Research
JF - The journal of investigative dermatology. Symposium proceedings / the Society for Investigative Dermatology, Inc. [and] European Society for Dermatological Research
IS - 2
ER -