人们早已知道，空气污染与呼吸系统疾病、心血管问题、发育不足以及肺癌等存在关联。加拿大科学家近日研究发现，空气污染还会增加小鼠精子的DNA突变。这一发现无疑将提升人们对空气污染影响人类健康和生育力的关注。相关论文1月14日在线发表于美国《国家科学院院刊》(PNAS)上。
领导此次研究的是加拿大卫生署(Health Canada)的Carole Yauk。她和同事将小鼠饲养在空气污染的加拿大汉密尔顿港钢厂和高速公路附近，结果发现，与对照组相比，污染区的小鼠精子DNA变异要多出60%多，DNA链断裂和甲基化也更多。
美国约翰·霍普金斯大学的流行病学家Jonathan Samet表示，“之前有科学家研究过污染与生殖的关系，不过大多关注的都是女性怀孕，而不是对男性的影响。”此次研究则是首次监测空气污染造成雄性小鼠精子DNA损伤的直接证据。Samet认为，接下来的研究是很重要的，即检验是否可将这一结果类推至人类。
理论上来说，精子的这些变异会改变后代小鼠的基因表达和功能，不过还未得到直接验证。另外，空气污染导致DNA损伤的具体机制也尚不清楚。
研究人员随后检测了多环芳烃类化合物对小鼠DNA的影响，这类化合物已知会导致突变并且在汉密尔顿区富集，但是结果显示它们与小鼠精子DNA损伤并无关联。
研究合作者、加拿大雷吉纳大学(University of Regina)生物学家Christopher Somers认为，这说明了这些变异可能是对颗粒污染更一般的反应。Samet说：“如果机制确实是这样的，那么此次结果就应该可以适用于其它来源的污染，而不仅仅是钢厂。”(科学网梅进/编译)
生物谷推荐英文原文：
Published online before print January 14, 2008, 10.1073/pnas.0705896105
PNAS | January 15, 2008 | vol. 105 | no. 2 | 605-610
BIOLOGICAL SCIENCES / GENETICS
Germ-line mutations, DNA damage, and global hypermethylation in mice exposed to particulate air pollution in an urban/industrial location
Carole Yauk*,, Aris Polyzos*, Andrea Rowan-Carroll*, Christopher M. Somers,, Roger W. Godschalk¶, Frederik J. Van Schooten¶, M. Lynn Berndt*, Igor P. Pogribny||, Igor Koturbash**, Andrew Williams, George R. Douglas*, and Olga Kovalchuk**
*Environmental and Occupational Toxicology Division, HECSB, Ottawa, ON, Canada K1A 0K9; Department of Biology, McMaster University, 1280 Main Street West, Hamilton, ON, Canada L8S 4K1; ¶Nutrition and Toxicology Research Institute Maastricht, NUTRIM, Department of Health Risk Analysis and Toxicology, Maastricht University, 6200 MD, PO Box 616, Maastricht, The Netherlands; ||Division of Biochemical Toxicology, National Center for Toxicological Research, Jefferson, AR 72079; **Department of Biological Sciences, University of Lethbridge, 4401 University Drive, Lethbridge, Alta., Canada T1K 3M4; and Biostatistics and Epidemiology Division, Healthy Environments and Consumer Safety Branch, Ottawa, ON, Canada K1A 0K9
Edited by James E. Cleaver, University of California, San Francisco, CA, and approved November 20, 2007 (received for review June 25, 2007)
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.
DNA adducts | DNA strand breaks | tandem repeat mutation
