Germ-line mutations, DNA damage, and global hypermethylation in mice exposed to particulate air pollution in an urban/industrial location
Germ-line mutations, DNA damage, and global hypermethylation in mice exposed to particulate air pollution in an urban/industrial location
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DOI：
10.1073/pnas.0705896105
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发表时间：
2008-01-15
影响因子：
11.1
通讯作者：
Kovalchuk, Olga
中科院分区：
文献类型：
--
作者：
Yauk, Carole;Polyzos, Aris;Kovalchuk, Olga
空气微粒污染很普遍，但我们对暴露在其中对健康的长期影响知之甚少。我们研究了暴露于工业/城市环境中颗粒空气污染的雄性小鼠配子的DNA损伤、突变和甲基化。C57BL/CBA小鼠暴露于两家综合钢铁厂和一条主要高速公路附近的环境空气中，对照组小鼠呼吸高效空气微粒（HEPA）过滤的环境空气。扩增简单串联重复序列（ESTR）位点的PCR分析显示，与hepa过滤的空气相比，暴露在环境空气中10周后休息6周的小鼠精子突变频率增加了1.6倍，这表明在精原干细胞中诱导了突变。暴露3周或10周后收集的DNA没有显示出突变频率增加。在睾丸样本中，大量DNA加合物低于检测阈值，表明DNA反应性化学物质不会到达生殖系并导致ESTR突变。相比之下，DNA链断裂在第3周和第10周升高，可能是由于暴露于颗粒和相关的空气污染物引起的氧化应激。相对于hepa过滤的空气，小鼠呼吸环境中的精子DNA高度甲基化，并且这种变化在去除环境暴露后持续存在。种系DNA突变频率的增加可能导致遗传组成和疾病的种群水平变化。甲基化的变化可以对染色质结构、基因表达和基因组稳定性产生广泛的影响。潜在的健康影响值得进一步广泛调查。
Particulate air pollution is widespread, yet we have little understanding of the long-term health implications associated with exposure. We investigated DNA damage, mutation, and methylation in gametes of male mice exposed to particulate air pollution in an industrial/urban environment. C57BL/CBA mice were exposed in situ to ambient air near two integrated steel mills and a major highway, alongside control mice breathing high-efficiency air particulate (HEPA) filtered ambient air. PCR analysis of an expanded simple tandem repeat (ESTR) locus revealed a 1.6-fold increase in sperm mutation frequency in mice exposed to ambient air for 10 wks, followed by a 6-wk break, compared with HEPA-filtered air, indicating that mutations were induced in spermatogonial stem cells. DNA collected after 3 or 10 wks of exposure did not exhibit increased mutation frequency. Bulky DNA adducts were below the detection threshold in testes samples, suggesting that DNA reactive chemicals do not reach the germ line and cause ESTR mutation. In contrast, DNA strand breaks were elevated at 3 and 10 wks, possibly resulting from oxidative stress arising from exposure to particles and associated airborne pollutants. Sperm DNA was hypermethylated in mice breathing ambient relative to HEPA-filtered air and this change persisted following removal from the environmental exposure. Increased germ-line DNA mutation frequencies may cause population-level changes in genetic composition and disease. Changes in methylation can have widespread repercussions for chromatin structure, gene expression and genome stability. Potential health effects warrant extensive further investigation.