Spectrum of mutations induced by sunlight

阳光诱导的突变谱

• 批准号: 03671052
• 负责人: NEGISHI Kazuo
• 金额: $ 1.28万
• 依托单位: Okayama 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: 1991
• 资助国家: 日本
• 起止时间: 1991 至 1992
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-03671052/
• 关键词: Sunlight; Near UV; Transversion; Mutation spectrum; 8-oxoguanine; M13mp2 phage; Oxidative damages; UVB; 太陽光; M13ファ-ジ; 突然変異; スペクトラム; トランスバ-ジョン; 8ーヒドロキシグアニン

Sunlight is well known to be mutagenic and carcinogenic. The genetic effects of sunlight are believed to be induced by pyrimidine photoproducts produced by the action of ultraviolet portion of sunlight. However, it is still unclear whether DNA lesions other than pyrimidine photoproducts are also involved in sunlight mutagenesis and carcinogenesis. We have analyzed mutagenic potential of sunlight on single-stranded DNA phage M13mp2 with the lacZETAalpha region of the DNA as target, using an SOS-deficient recA^- strain and an SOS-induced rec^+ strain of Escherichia coli as hosts. Exposure to sunlight caused mutations ; about 10-fold increase in the mutation frequencies were observed with the use of both hosts. When the SOS functions were induced in the rec^+ host, CSH50, the mutation frequencies increased another 10-fold over those obtained with the host lacking the SOS functions. DNA sequence analysis of these mutants showed that most of the mutations were transversions, either G to C or G to T. Furthermore, 59 % of the identified sequence changes in the SOS^- host and 40 % of those in the SOS-induced host were G-to-C transversions. These results suggest the possibility that an unidentified modification of guanine in the DNA is produced by sunlight. We analyzed 8-hydroxydeoxyguanosine (8-oh-G) contents in M13mp2 DNA before and after sunlight exposure. The content of 8-oh-G increased 3- to 5-fold during a 5 h exposure to sunlight. UVB irradiation using 312 nm light showed a dose-dependent increase in the 8-oh-G contents. Additional experiments suggested that UVA portion of sunlight is also involved. However, the increase in the contents of 8-oh-G was only several-fold over the controls. Therefore, a damaged guanine other than 8-oh-G also may serve as a mutagenic lesion in sunlight mutagenesis.

众所周知，阳光具有致突变性和致癌性。阳光的遗传效应被认为是由阳光的紫外线部分作用产生的嘧啶光产物诱导的。然而，目前还不清楚嘧啶光产物以外的DNA损伤是否也参与了阳光诱变和致癌作用。我们分析了太阳光对单链DNA噬菌体M13 mp2的诱变潜力，并以DNA的lacZETA α区为靶标，使用大肠杆菌的SOS缺陷型recA^-菌株和SOS诱导型recA ^+菌株作为宿主。暴露于阳光下引起突变;使用两种宿主观察到突变频率增加约10倍。当在rec^+宿主CSH 50中诱导SOS功能时，突变频率比在缺乏SOS功能的宿主中获得的突变频率增加了10倍。对这些突变体的DNA序列分析表明，大多数突变是颠换，要么是G到C，要么是G到T。此外，在SOS^-宿主和SOS诱导的宿主中，分别有59%和40%的序列变化是G到C的颠换。这些结果表明，DNA中鸟嘌呤的一种未知修饰可能是由阳光产生的。我们分析了阳光照射前后M13 mp2 DNA中8-羟基脱氧鸟苷（8-oh-G）的含量。8-oh-G的含量增加3- 5倍，在5小时暴露于阳光下。用312 nm的紫外线照射，8-oh-G含量呈剂量依赖性增加。其他实验表明，太阳光的UVA部分也参与其中。然而，8-oh-G含量的增加仅是对照的几倍。因此，除了8-oh-G之外，受损的鸟嘌呤也可能在阳光诱变中起到致突变作用。

项目成果

Kazuo Negishi, Yuka Fujiwara and Weidong Hao: "DNA damages and mutations on phage M13mp2 exposed to sunlight" Book of Abstracts, Sixth International Conference on Environmental Mutagens.

Kazuo Negishi、Yuka Fujiwara 和 Weidonghao：“暴露于阳光下的噬菌体 M13mp2 的 DNA 损伤和突变”摘要集，第六届国际环境诱变剂会议。

K,Negishi,Y.Fujiwara and H.Hao: "DNA damages and mutations on phage M13mp2 exposed to sunlight" Book of Adstracts,6th ICEM. 378 (1993)

K，Negishi，Y.Fujiwara 和 H.Hao：“暴露于阳光下的噬菌体 M13mp2 的 DNA 损伤和突变”Book of Adstracts，第 6 届 ICEM。

H.Hayatsu: "Permanganate oxidation of nucleic acid components:a reinvestigation." Nucleic Acids Symposium Sereis No.25. 77-78 (1991)

H.Hayatsu：“核酸成分的高锰酸盐氧化：重新研究。”

K.Negishi: "Spectrum of mutations in singleーstranded DNA phage M13mp2 exposed to sunlight:Predominance of GーtoーCーtransversion"

K.Negishi：“暴露在阳光下的单链 DNA 噬菌体 M13mp2 的突变谱：G 到 C 转换的优势”

K.NEGISHI and W.HAO: "Spectrum of mutations in single-stranded DNA phage M13mp2 exposed to sunlight:predominance of G-to-C transversion" Carcinogenesis. 13. 1615-1618 (1992)

K.NEGISHI 和 W.HAO：“暴露于阳光下的单链 DNA 噬菌体 M13mp2 的突变谱：G 到 C 转换的优势”致癌作用。