A new aspect in DNA damages induced by sunlight-possible involvement of damages on guanine and 5-methylcytosine

阳光引起的DNA损伤的一个新方面——可能涉及鸟嘌呤和5-甲基胞嘧啶的损伤

• 批准号: 07839010
• 负责人: NEGISHI Kazuo
• 金额: $ 1.66万
• 依托单位: Okayama University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1995
• 资助国家: 日本
• 起止时间: 1995 至 1996
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-07839010/
• 关键词: Phage M13mp2; Mutagenesis; %-methylcytosine; UV light; Sunlight; 8-oxoguanine; Skin cancer; mutM; 光水和物; UVB; シトシン; グアニン; 単色光照射; 光二量体

It is well known that sunlight is both carcinogenic and mutagenic. However, nature of the DNA damages causing mutation and cancer have yet well understood. Here we tried to analyzed DNA damages induced by sunlight mainly using sunlight itsel f as a UV source. In this project we focused on the damages of guanine and 5-methylcytosine.Previously we found that sunlight induced G-to-C transition in phage M13mp2. This mutagenic specificity indicates the formation of guanine damages by sunlight exposure on the phage. In constrast, UVB irradiation caused mutations at pyrimidines. Therefore, we postulate that DNA damaging effects of sunlight is different from those of UVB.Next we analyzed the mutM sensitivity of the possible guanine damages caused by sunlight exposure. There was found no difference in the mutability of M13mp2 between in the assays on mutM^+ host and mutM^- host. This results indicated that the mutagenic leison were not able to be repaired by mutM system.We also studied photoreaction on 5-methylcytosine. This base has much greater absorption coefficient at wavelengths over 300 nm. The UV light around 300 nm is believed to be most important for the genotoxic effects of sunlight. However its photodegaradabilty has not been compared extensively with cytosine and thymidine. As model compounds, photoreaction of 5-methyldeoxycytidine (mC) and dCpdmC were studied. Upon irradiation by germicidal lamp peaking at 254 nm, deoxycytidine seemed to be converted to deoxycytidine hydrate as reported in the literature. 5-methyldeoxycytidine also degraded at a slower rate than deoxycytidine. Next reactivities of, a dinucleoside monophosphate, was analyzed. Two major peaks among the products from dCpdmC seemed to be 6-4 photoproduct and its dewar isomer.

众所周知，阳光既致癌又致突变。然而，导致突变和癌症的DNA损伤的性质尚未得到很好的理解。本文主要以太阳光本身为紫外光源，分析了太阳光对DNA的损伤作用。本课题主要研究鸟嘌呤和5-甲基胞嘧啶对噬菌体的损伤作用。这种致突变特异性表明阳光照射在噬菌体上形成鸟嘌呤损伤。UVB照射引起的嘧啶突变。因此，我们推测，阳光的DNA损伤效应是不同的UVB。接下来，我们分析了mutM敏感性的可能的鸟嘌呤损伤所造成的阳光照射。在mutM^+宿主和mutM^-宿主的检测中，没有发现M13 mp2的突变性有任何差异。本实验还研究了5-甲基胞嘧啶的光反应。该基底在超过300 nm的波长处具有大得多的吸收系数。300 nm左右的紫外线被认为是最重要的遗传毒性作用的阳光。然而，其光降解性尚未与胞嘧啶和胸苷进行广泛比较。以5-甲基脱氧胞苷（mC）和dCpdmC为模型化合物，研究了它们的光反应.如文献中所报道的，在用峰值为254 nm的杀菌灯照射时，脱氧胞苷似乎转化为脱氧胞苷水合物。5-甲基脱氧胞苷的降解速率也比脱氧胞苷慢。接下来分析了二核苷单磷酸的反应性。在dCpdmC的产物中，有两个主要峰似乎是6-4光产物及其杜瓦异构体。

项目成果

W.H.Hao: "Spectra of UVB-induced mutations in single stranded DNA phage M13mp2" Mutation Res. (Selected Abstracts for JEMS). (in press). (1996)

W.H.Hao：“单链 DNA 噬菌体 M13mp2 中 UVB 诱导突变的光谱”突变研究。

V.N.Noskov他: "HAMI,the gene controlling 6-N-hydroxylaminopurine sensitivity and mutagenesis in the Saccharomyces cerevisiae" Yeast. 12. 17-29 (1996)

V.N.Noskov 等人：“HAMI，酿酒酵母中控制 6-N-羟氨基嘌呤敏感性和诱变的基因”酵母。

V.N.Noskov, et al.: "HAM1, the gene controlling 6-N-hydroxylaminopurine sensitivity and mutagenesis in the Saccharomyces cerevisiae" Yeast. 12. 17-29 (1996)

V.N.Noskov 等人：“HAM1，控制酿酒酵母中 6-N-羟氨基嘌呤敏感性和诱变的基因”酵母。

K.Hiramoto他: "Induction of DNA recombination by activated 3-amino-1-methyl-5H-pyrido[4,3-b]indole (Trp-P-2)" Jpn.J.Cancer Res.86. 155-159 (1995)

K. Hiramoto 等人：“通过活化的 3-氨基-1-甲基-5H-吡啶并[4,3-b]吲哚 (Trp-P-2) 诱导 DNA 重组”Jpn.J.Cancer Res.86。 155- 159 (1995)

K.Negishi他: "The mechanism of mutation induction by a hydrogen bond ambivalent,bicyclic N4-oxy-2′-deoxycytidine in Escherichia coli" Nucleic Acids Res.(印刷中). (1997)

K. Negishi 等人：“大肠杆菌中双环 N4-氧-2-脱氧胞苷诱导突变的机制”《核酸研究》（出版中）。