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

比较了具有不同DNA修复机制的细胞之间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G：C向A：T转变突变，DNA修复缺陷型着色性干皮病(XP)细胞的突变高于正常人和小鼠细胞。这表明，正常人和小鼠细胞在紫外线照射下，无论其DNA修复机制不同，都经历了相似类型的突变。PCR-SSCP分析显示，在XP患者阳光暴露区发生的皮肤肿瘤中，约有一半存在p53基因突变。最常见的突变类型是5‘-TC和5’-CC双嘧啶序列的C-T转变，类似于体外紫外线诱导的突变类型。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生发展中起着重要作用。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的5‘-TC或5’-CC的C到T转变。这些结果表明，紫外线诱导的突变对ras基因具有转化活性，但ras基因突变不会导致XP患者皮肤肿瘤的发生。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基因的突变类型反映为紫外线诱导的突变类型。

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.