Nishigori C, Wang S, Miyakoshi J, Sato M, Tsukada T, Yagi T, Imamura S, Takebe H
Department of Experimental Radiology, Faculty of Medicine, Kyoto University, Japan.
Proc Natl Acad Sci U S A. 1994 Jul 19;91(15):7189-93. doi: 10.1073/pnas.91.15.7189.
Mutations in ras oncogenes were detected in cultured cells of mouse skin tumors induced by near-UV irradiation. DNA extracted from the UV-induced tumor cells was transfected to golden hamster embryo cells, and focus-forming ability was confirmed in 22 of 26 cell strains, 15 of which had the repetitive mouse sequence. Mouse ras genes were detected in 10 of these 22 cell strains. Point mutations in the ras genes were at Ha-ras codon 13 (GGC-->GTC in two strains, GGC-->AGC in one strain), Ki-ras codon 61 (CAA-->GAA in two strains), and N-ras codon 61 (CAA-->CAT in two strains, CAA-->AAA in two strains). In one tumor cell strain no base change was directed. Most mutations occurred at dipyrimidine sites. Pyrimidine dimers or pyrimidine(6-4)pyrimidone photoproducts are the likely cause of the skin cancers. The base change occurred preferentially at G.C base pairs, and transversions predominated.
在近紫外线照射诱导的小鼠皮肤肿瘤的培养细胞中检测到ras癌基因的突变。从紫外线诱导的肿瘤细胞中提取的DNA被转染到金黄地鼠胚胎细胞中,在26个细胞株中的22个中证实了集落形成能力,其中15个具有重复的小鼠序列。在这22个细胞株中的10个中检测到小鼠ras基因。ras基因中的点突变发生在Ha-ras密码子13(两个株系中GGC→GTC,一个株系中GGC→AGC)、Ki-ras密码子61(两个株系中CAA→GAA)和N-ras密码子61(两个株系中CAA→CAT,两个株系中CAA→AAA)。在一个肿瘤细胞株系中未发现碱基变化。大多数突变发生在二嘧啶位点。嘧啶二聚体或嘧啶(6-4)嘧啶酮光产物可能是皮肤癌的病因。碱基变化优先发生在G.C碱基对,且转换占主导。