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利用穿梭载体测定特定波长太阳UVB(313纳米)辐射在哺乳动物细胞中诱导的突变谱。

Determination of the spectrum of mutations induced by defined-wavelength solar UVB (313-nm) radiation in mammalian cells by use of a shuttle vector.

作者信息

Keyse S M, Amaudruz F, Tyrrell R M

机构信息

Swiss Institute for Experimental Cancer Research, Epalinges.

出版信息

Mol Cell Biol. 1988 Dec;8(12):5425-31. doi: 10.1128/mcb.8.12.5425-5431.1988.

Abstract

Mutations induced by UVB (313-nm) radiation, a wavelength in the region of peak effectiveness for sunlight-induced skin cancer in humans, have been analyzed at the sequence level in simian cells by using a plasmid shuttle vector (pZ189). We find that significant differences exist between the types of mutations induced by this solar wavelength and those induced by nonsolar UVC (254-nm) radiation. Compared with 254-nm radiation, 313-nm radiation induces more deletions and insertions in the region sequenced. In addition, although the types of base substitutions induced by the two wavelengths are broadly similar (in both cases, the majority of changes occur at G-C base pairs and the G-C to A-T transition is predominant), an analysis of the distribution of these base changes within the supF gene following irradiation at 313 nm reveals additional hot spots for mutation not seen after irradiation at 254 nm. These hot spots are shown to arise predominantly at sites of mutations involving multiple base changes, a class of mutations which arises more frequently at the longer solar wavelength. Lastly, we observed that most of the sites at which mutational hot spots arise after both UVC and UVB irradiation of the shuttle vector are also sites at which mutations arise spontaneously. Thus, a common mechanism may be involved in determining the site specificity of mutations, in which the DNA structure may be a more important determinant than the positions of DNA photoproducts.

摘要

通过使用质粒穿梭载体(pZ189),在猴细胞的序列水平上分析了由UVB(313纳米)辐射诱导的突变,UVB是人类阳光诱导皮肤癌的最有效波长区域内的一种波长。我们发现,这种太阳波长诱导的突变类型与非太阳UVC(254纳米)辐射诱导的突变类型之间存在显著差异。与254纳米辐射相比,313纳米辐射在测序区域诱导更多的缺失和插入。此外,尽管两种波长诱导的碱基替换类型大致相似(在两种情况下,大多数变化发生在G-C碱基对,且G-C到A-T的转换占主导),但对313纳米照射后supF基因内这些碱基变化分布的分析揭示了254纳米照射后未观察到的额外突变热点。这些热点主要出现在涉及多个碱基变化的突变位点,这类突变在较长的太阳波长下更频繁出现。最后,我们观察到,穿梭载体在UVC和UVB照射后出现突变热点的大多数位点也是自发突变出现的位点。因此,可能存在一种共同机制来决定突变的位点特异性,其中DNA结构可能比DNA光产物的位置更重要。

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