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

基本信息

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

项目摘要

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，阳光既具有致癌和诱变。但是，DNA损害的性质引起突变和癌症尚未得到充分理解。在这里，我们试图分析阳光主要使用Sunlight Itsel F作为UV来源引起的DNA损害。在这个项目中，我们专注于鸟嘌呤和5-甲基胞嘧啶的损害。我们发现，阳光在噬菌体M13MP2中诱导了G-C-C转变。这种诱变特异性表明，噬菌体上的阳光暴露在鸟嘌呤的形成中。在约束中，UVB照射在嘧啶上引起突变。因此，我们假设阳光的DNA损害效应与UVB的损害作用不同。我们分析了阳光暴露造成的鸟嘌呤损害的mutM敏感性。在MUTM^+ host和mutm^ - 宿主的测定中，M13MP2的突变性没有差异。该结果表明，诱变的Leison无法通过MUTM系统修复。我们还研究了5-甲基胞嘧啶的光反应。该碱基在300 nm以上的波长下具有更大的吸收系数。据信，大约300 nm的紫外线对于阳光的遗传毒性作用最为重要。但是，尚未将其光去加仑属与胞嘧啶和胸苷进行广泛的比较。作为模型化合物，研究了5-甲基氧基胞丁胺（MC）和DCPDMC的光反应。在254 nm处峰值峰值的辐照后，如文献中报道的那样，脱氧胞苷似乎已转化为脱氧胞苷水合物。 5-甲基氧基辛丁定的降解也比脱氧胞苷的降解较慢。分析了下一个二核苷单磷酸盐的反应率。 DCPDMC产物中的两个主要峰似乎是6-4光产物及其露水异构体。