Particulate matter inhibits DNA repair and enhances mutagenesis.
Particulate matter inhibits DNA repair and enhances mutagenesis.
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DOI：
10.1016/j.mrgentox.2008.08.015
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发表时间：
2008-12-08
影响因子：
1.9
通讯作者：
Tang, Moon-shong
中科院分区：
文献类型：
--
作者：
Mehta, Manju;Chen, Lung-Chi;Gordon, Terry;Rom, William;Tang, Moon-shong
暴露于环境空气污染与包括肺癌在内的不利健康影响有关。最近的一项流行病学研究证实，长期暴露于PM2.5平均环境浓度每升高10 μg/m3，就与约8%的肺癌死亡率相关。然而，PM如何促进肺癌发生的潜在机制仍有待阐明。我们最近发现过渡金属如镍和铬以及氧化应激诱导的脂质过氧化代谢物如醛可以极大地抑制核苷酸切除修复（NER）并增强致癌物质诱导的突变。由于PM含有丰富的金属和醛，并可诱导氧化应激，我们通过体外DNA修复合成和宿主细胞再激活实验来测试PM对培养的人肺细胞DNA修复能力的影响。我们发现PM对紫外线（UV）光和苯并(a)芘二醇环氧化物（BPDE）诱导的人肺细胞DNA损伤有很大的抑制作用。我们进一步证明PM暴露可以显著增加自发和紫外线诱导的诱变。这些结果表明，PM的致癌性可能是通过抑制DNA修复和增强DNA复制错误的联合作用来实现的。
Exposure to ambient air pollution has been associated with adverse health effects including lung cancer. A recent epidemiology study has established that each 10 μg/m3 elevation in long term exposure to average PM2.5 ambient concentration was associated with approximately 8% of lung cancer mortality. The underlying mechanisms of how PM contributes to lung carcinogenesis, however, remain to be elucidated. We have recently found that transition metals such as nickel and chromium and oxidative stress induced lipid peroxidation metabolites such as aldehydes can greatly inhibit nucleotide excision repair (NER) and enhance carcinogen-induced mutations. Because PM is rich in metal and aldehyde content and can induce oxidative stress, we tested the effect of PM on DNA repair capacity in cultured human lung cells using in vitro DNA repair synthesis and host cell reactivation assays. We found that PM greatly inhibits NER for ultraviolet (UV) light and benzo(a)pyrene diol epoxide (BPDE) induced DNA damage in human lung cells. We further demonstrated that PM exposure can significantly increase both spontaneous and UV-induced mutagenesis. These results together suggest that the carcinogenicity of PM may act through its combined effect on suppression of DNA repair and enhancement of DNA replication errors.
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影响因子：
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