人們?cè)缫阎?，空氣污染與呼吸系統(tǒng)疾病、心血管問題,、發(fā)育不足以及肺癌等存在關(guān)聯(lián),。加拿大科學(xué)家近日研究發(fā)現(xiàn),，空氣污染還會(huì)增加小鼠精子的DNA突變。這一發(fā)現(xiàn)無疑將提升人們對(duì)空氣污染影響人類健康和生育力的關(guān)注,。相關(guān)論文1月14日在線發(fā)表于美國(guó)《國(guó)家科學(xué)院院刊》(PNAS)上,。
領(lǐng)導(dǎo)此次研究的是加拿大衛(wèi)生署(Health Canada)的Carole Yauk。她和同事將小鼠飼養(yǎng)在空氣污染的加拿大漢密爾頓港鋼廠和高速公路附近,，結(jié)果發(fā)現(xiàn),，與對(duì)照組相比，污染區(qū)的小鼠精子DNA變異要多出60%多,，DNA鏈斷裂和甲基化也更多,。
美國(guó)約翰·霍普金斯大學(xué)的流行病學(xué)家Jonathan Samet表示，“之前有科學(xué)家研究過污染與生殖的關(guān)系,，不過大多關(guān)注的都是女性懷孕,，而不是對(duì)男性的影響。”此次研究則是首次監(jiān)測(cè)空氣污染造成雄性小鼠精子DNA損傷的直接證據(jù),。Samet認(rèn)為,，接下來的研究是很重要的，即檢驗(yàn)是否可將這一結(jié)果類推至人類,。
理論上來說,，精子的這些變異會(huì)改變后代小鼠的基因表達(dá)和功能，不過還未得到直接驗(yàn)證,。另外,，空氣污染導(dǎo)致DNA損傷的具體機(jī)制也尚不清楚。
研究人員隨后檢測(cè)了多環(huán)芳烴類化合物對(duì)小鼠DNA的影響,，這類化合物已知會(huì)導(dǎo)致突變并且在漢密爾頓區(qū)富集,，但是結(jié)果顯示它們與小鼠精子DNA損傷并無關(guān)聯(lián)。
研究合作者,、加拿大雷吉納大學(xué)(University of Regina)生物學(xué)家Christopher Somers認(rèn)為,，這說明了這些變異可能是對(duì)顆粒污染更一般的反應(yīng)。Samet說：“如果機(jī)制確實(shí)是這樣的,，那么此次結(jié)果就應(yīng)該可以適用于其它來源的污染,，而不僅僅是鋼廠。”(科學(xué)網(wǎng)梅進(jìn)/編譯)
生物谷推薦英文原文：
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
