UV-induced DNA damage in carcinogenesis and its repair.
The purpose of this study is to ask what kind of DNA damage is involved in UV carcinogenesis. Firstly, ras gene alterations were analyzed in UV-induced mice skin cancers. Five types of base changes resulting in activated ras were detected in nine UV-induced skin cancers. Unexpectedly, transversions predominated, whereas previous findings using shuttle vectors indicated that UVC predominantly causes transition-type mutations, which implies the involvement of DNA damage other than dimers in UV carcinogenesis in vivo, in the presence of endogenous photosensitizers. Secondly, we detected mutations both in p53 and ras of skin cancers from patients with xeroderma pigmentosum (XP). Fifty percent of non-melanoma-skin cancers (NMSCs) from XP patients had mutations in p53. The mutation occurred preferentially at CC sites and transitions predominated for p53, whereas ras mutations were far less frequent over the same samples, indicating that DNA damage caused by sunlight rarely hits the crucial sites of ras. Lastly, p53 mutations on NMSCs were compared between sun-exposed area and non/less sun-exposed area. The frequency of p53 mutations between these two groups were almost comparable. However, 67% had the transition at dipyrimidine sites in NMSCs from sun-exposed area, whereas only 20% had the same type of mutations from non/less exposed area (P<0.05).
Nishigori
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Department of Dermatology, Graduate School of Medicine, Kyoto University, 54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto, Japan. chikako@kuhp.kyoto-u.ac.jp
D000818:Animals; D004249:DNA Damage; D004260:DNA Repair; D016158:Genes, p53 / Q000528:radiation effects; D011905:Genes, ras / Q000528:radiation effects; D006801:Humans; D051379:Mice; D009154:Mutation; D009381:Neoplasms, Radiation-Induced / Q000209:etiology* / Q000235:genetics / Q000378:metabolism; D012878:Skin Neoplasms / Q000209:etiology / Q000235:genetics / Q000378:metabolism; D014466:Ultraviolet Rays / Q000009:adverse effects*; D014983:Xeroderma Pigmentosum / Q000235:genetics