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首页> 外文OA文献 >UVA radiation is highly mutagenic in cells that are unable to repair 7,8-dihydro-8-oxoguanine in Saccharomyces cerevisiae
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UVA radiation is highly mutagenic in cells that are unable to repair 7,8-dihydro-8-oxoguanine in Saccharomyces cerevisiae

机译：在无法修复啤酒酵母中的7,8-二氢-8-氧鸟嘌呤的细胞中，UVA辐射具有高度致突变性。

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UVA (320-400 nm) radiation constitutes >90% of the environmentally relevant solar UV radiation, and it has been proposed to have a role in skin cancer and aging. Because of the popularity of UVA tanning beds and prolonged periods of sunbathing, the potential deleterious effect of UVA has emerged as a source of concern for public health. Although generally accepted, the impact of DNA damage on the cytotoxic, mutagenic, and carcinogenic effect of UVA radiation remains unclear. In the present study, we investigated the sensitivity of a panel of yeast mutants affected in the processing of DNA damage to the lethal and mutagenic effect of UVA radiation. The data show that none of the major DNA repair pathways, such as base excision repair, nucleotide excision repair, homologous recombination, and postreplication repair, efficiently protect yeast from the lethal action of UVA radiation. In contrast, the results show that the Ogg1 DNA glycosylase efficiently prevents UVA-induced mutagenesis, suggesting the formation of oxidized guanine residues. Furthermore, sequence analysis of UVA-induced canavanine-resistant mutations reveals a bias in favor of GC→TA events when compared with spontaneous or H2O2-, UVC-, and γ-ray- induced canavanine-resistant mutations in the WT strain. Taken together, our data point out a major role of oxidative DNA damage, mostly 7,8-dihydro-8-oxoguanine, in the genotoxicity of UVA radiation in the yeast Saccharomyces cerevisiae. Therefore, the capacity of skin cells to repair 7,8-dihydro-8-oxoguanine may be a key parameter in the mutagenic and carcinogenic effect of UVA radiation in humans.
机译：UVA（320-400 nm）辐射构成与环境有关的太阳UV辐射的> 90％，并且已提出在皮肤癌和衰老中起作用。由于UVA晒黑床的普及以及长时间的日光浴，UVA的潜在有害作用已成为引起公众健康关注的原因。尽管被普遍接受，但DNA损伤对UVA辐射的细胞毒性，诱变和致癌作用的影响尚不清楚。在本研究中，我们调查了一组在DNA损伤处理中受到影响的酵母突变体对UVA辐射的致死和诱变作用的敏感性。数据显示，主要的DNA修复途径（如碱基切除修复，核苷酸切除修复，同源重组和复制后修复）均不能有效地保护酵母免受UVA辐射的致命作用。相比之下，结果表明Ogg1 DNA糖基化酶有效地阻止了UVA诱导的诱变，表明形成了氧化鸟嘌呤残基。此外，与WT菌株中自发的或H2O2-，UVC-和γ射线诱导的卡瓦因抗性突变相比，对UVA诱导的卡瓦因抗性突变的序列分析显示，偏向于GC→TA事件。两者合计，我们的数据指出了氧化性DNA损伤（主要是7,8-二氢-8-氧鸟嘌呤）在酿酒酵母中对UVA辐射的遗传毒性中起主要作用。因此，皮肤细胞修复7,8-二氢-8-氧鸟嘌呤的能力可能是UVA辐射对人类诱变和致癌作用的关键参数。

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