Qualitative difference in radiation-induced mutations by the difference in DNA repair mechanisms among cells.

细胞间 DNA 修复机制的差异导致辐射诱发突变的质的差异。

• 批准号: 04680211
• 负责人: YAGI Takashi
• 金额: $ 1.6万
• 依托单位: KYOTO UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1992
• 资助国家: 日本
• 起止时间: 1992 至 1993
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-04680211/
• 关键词: DNA repair; Mutation; radiation; Ultraviolet; Xeroderma pigmentosum; Tumor suppressor gene; 高発がん性遺伝病

The frequency and type of radiation-induced mutations were compared among the cells having different DNA repair mechanisms and between in vitro and in vivo. UV mainly induced G : C to A : T transition mutation in all cells, and the mutation was higher in DNA repair-deficient xeroderma pigmentosum (XP) cells than in normal human and mouse cells. This shows that normal human and mouse cells sustained the similar type of mutation by UV regardless of their different DNA repair mechanism.The PCR-SSCP analysis revealed that about half of skin tumors developed in sun-exposed area of XP patients have mutations in p53 gene. The most frequent type of mutation was the C to T transition at 5'-TC and 5'-CC dipyrimidine sequences, which were similar to the type of UV-induced mutation in vitro. No mutation was detected in skin tumors from the XP patients. These results indicate that the mutations in p53 gene were induced by sunlight UV, and not ras genes but the p53 gene plays an important role in skin tumor development.Transfection of the normal Ha-ras sequence irradiated with UV produced transformed-foci in mouse BALB3T3 cells. The ras sequences retrieved from the transformed-foci have point mutations. The most frequent type of mutation was the C to T transition at 5'-TC or 5'-CC in codons 12, 13 and 60 in the ras sequence. These results indicate that UV induces mutations which confer transforming activity to ras genes but the ras gene mutations do not lead to tumor development in the skin of XP patients.This study showed that the different type of mutation were induced by UV between the cells with different DNA repair ability, and the type of mutations found in p53 gene in skin tumors in XP patients is reflected to the type of UV-induced mutation.

比较了具有不同 DNA 修复机制的细胞以及体外和体内辐射诱导突变的频率和类型。紫外线主要诱导所有细胞中G:C向A:T的转变突变，且DNA修复缺陷性干皮病(XP)细胞中的突变高于正常人和小鼠细胞。这表明，尽管正常人和小鼠的DNA修复机制不同，但正常人和小鼠细胞在紫外线下都经历了相似类型的突变。PCR-SSCP分析显示，XP患者暴露于阳光区域的皮肤肿瘤中约有一半具有p53基因突变。最常见的突变类型是 5'-TC 和 5'-CC 二嘧啶序列的 C 到 T 转变，这与体外紫外线诱导的突变类型相似。 XP 患者的皮肤肿瘤中未检测到突变。这些结果表明p53基因的突变是由太阳光紫外线诱导的，而不是ras基因，而是p53基因在皮肤肿瘤的发展中起重要作用。转染经紫外线照射的正常Ha-ras序列在小鼠BALB3T3细胞中产生转化灶。从转化灶中检索到的 ras 序列具有点突变。最常见的突变类型是 ras 序列中密码子 12、13 和 60 中 5'-TC 或 5'-CC 处的 C 到 T 转变。这些结果表明，紫外线诱导突变，赋予ras基因转化活性，但ras基因突变不会导致XP患者皮肤中肿瘤的发生。本研究表明，紫外线在具有不同DNA修复能力的细胞之间诱导了不同类型的突变，XP患者皮肤肿瘤中p53基因中发现的突变类型反映了紫外线诱导的突变类型。

项目成果

Shinichi Moriwaki 森脇 真一: "A case of xeroderma pigmentosum complementation group F with newrological abnormalities" British Journal of Derma-tology. 128. 91-94 (1993)

Shinichi Moriwaki：“伴有新病学异常的着色性干皮病 F 组病例”英国皮肤学杂志 128. 91-94 (1993)。

Yagi,T. 八木孝司: "Similarity in the molecular profile of mutations induced by UV light in shuttle vector plasmids propagated in mouse and human cells" Mutagenesis. 9. 73-77 (1994)

Yagi, T. Takashi Yagi：“在小鼠和人类细胞中繁殖的穿梭载体质粒中由紫外线诱导的突变的分子谱的相似性” Mutagenesis。

Tatsumi-Miyajima,J.巽純子: "Analysis of mutations caused by DNA double-strand breaks produced by a restriction enzyme in shuttle vector plasmids propagated in ataxia telangiectasia cells." Mutation Research. 294. 317-323 (1993)

Tatsumi-Miyajima，J. Junko Tatsumi：“由在共济失调毛细血管扩张细胞中繁殖的穿梭载体质粒中的限制性酶产生的 DNA 双链断裂引起的突变分析。” 294. 317-323 (1993)。

Sato, M.et al.: "Ultraviolet-specific mutations in p53 gene in skin tumors in xeroderma pigmentosum patients." Cancer Research. 53. 2944-2946 (1993)

Sato, M.等人：“着色性干皮病患者皮肤肿瘤中 p53 基因的紫外线特异性突变。”

Yagi, T.et al.: "Similarity in the molecular profile of mutations induced by UV light in shuttle vector plasmids propaged in mouse and human cells." Mutagenesis. 9. 73-77 (1994)

Yagi, T.等人：“在小鼠和人类细胞中繁殖的穿梭载体质粒中，紫外线诱导的突变分子谱的相似性。”