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紫外线和近可见光辐射对人皮肤细胞中氧化性DNA碱基损伤的诱导作用。

Induction of oxidative DNA base damage in human skin cells by UV and near visible radiation.

作者信息

Kvam E, Tyrrell R M

机构信息

Swiss Institute for Experimental Cancer Research, Epalinges.

出版信息

Carcinogenesis. 1997 Dec;18(12):2379-84. doi: 10.1093/carcin/18.12.2379.

Abstract

The premutagenic oxidative DNA base damage, 7,8-dihydro-8-oxoguanine, is induced in human skin fibroblasts by monochromatic radiation ranging from a UVB wavelength (312 nm) up to wavelengths in the near visible (434 nm). The oxidative damage is not generated by absorption of radiation in DNA but rather by activation of photosensitizers generating genotoxic singlet oxygen species. The spectrum for the yield of the oxidative damage in confluent, non-growing, primary skin fibroblasts shows that it is UVA (above 334 nm) and near visible radiations which cause almost all of this guanine oxidation by natural sunlight in the fibroblast model. We estimate that the total amount of oxidation of guanine induced by sunlight in fibroblasts in the epidermis of the skin equals or exceeds the amount of the major type of direct DNA damage, cyclobutane pyrimidine dimers. In rapidly dividing lymphoblastoid cells, no oxidative guanine damage was induced. However, in melanoma cells almost as much damage as in non-growing fibroblasts (1.1 per 10(4) guanine bases after 1200 kJ/m2 UVA) was found. We conclude that oxidative DNA base damage can probably contribute to the induction of both non-melanoma and melanoma skin cancer by sunlight.

摘要

前诱变氧化DNA碱基损伤,即7,8 - 二氢 - 8 - 氧代鸟嘌呤,可由波长范围从UVB(312 nm)到近可见光(434 nm)的单色辐射在人皮肤成纤维细胞中诱导产生。这种氧化损伤并非由DNA吸收辐射产生,而是由产生基因毒性单线态氧物种的光敏剂激活所致。在汇合的、不生长的原代皮肤成纤维细胞中,氧化损伤产量的光谱表明,在成纤维细胞模型中,几乎所有这种鸟嘌呤氧化都是由UVA(334 nm以上)和近可见光辐射通过自然阳光引起的。我们估计,皮肤表皮成纤维细胞中阳光诱导的鸟嘌呤氧化总量等于或超过主要类型的直接DNA损伤——环丁烷嘧啶二聚体的量。在快速分裂的淋巴母细胞中,未诱导出氧化鸟嘌呤损伤。然而,在黑色素瘤细胞中,发现的损伤几乎与不生长的成纤维细胞中一样多(1200 kJ/m² UVA照射后每10⁴个鸟嘌呤碱基中有1.1个损伤)。我们得出结论,氧化DNA碱基损伤可能有助于阳光诱导非黑色素瘤和黑色素瘤皮肤癌。

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