Effect of Particulate Matter on DNA Deletions in Mice

颗粒物对小鼠 DNA 缺失的影响

• 批准号: 7347029
• 负责人: ROBERT H SCHIESTL
• 金额: $ 3.07万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-02-15 至 2009-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7347029
• 关键词: Acetylcysteine; Address; Affect; Air; Air Pollution; Antioxidants; Biological; Biological Assay; Breathing; Buthionine Sulfoximine; Cancer Etiology; Carcinogens; Chemicals; Cities; Collaborations; DNA; Diesel Exhaust; Environment; Epidemiologic Studies; Equilibrium; Exposure to; Frequencies; Generations; Genetic; Grant; Health; Heart Diseases; Home environment; Human; Individual; Inflammation; Institutes; Investigation; Lead; Light; Los Angeles; Lung; Malignant Neoplasms; Mexico; Mus; Nature; North America; Numbers; Nutritional; Oxidation-Reduction; Oxidative Stress; Particulate; Particulate Matter; Pneumonia; Process; Property; Recommendation; Research; Respiratory Tract Diseases; Risk Management; Time; Uncertainty; United States National Institutes of Health; Upper respiratory tract; base; buthionine; carcinogenesis; in vivo; mortality; particle

Mexico City is home to more than 18 million individuals who breathe the most polluted air in North America. Paniculate Matter (PM) contained in air pollution consists of a staggering number of known carcinogens and there is some epidemiological indication that exposure to PM causes cancer in people. We have shown in preliminary results that an exposure to diesel exhaust particles significantly increases the frequency of DNA deletions in mice. Genetic instability, in particular DNA deletions are involved in the etiology of cancer. In addition, many other carcinogens induce such deletions, several of them through an oxidative mechanism. Aim 1 is to determine whether PM from different parts of Mexico City increase the frequency of DNA deletions in mice. The findings could shed mechanistic light on the potential association between PM exposure and cancer, which is currently unknown. Since oxidative stress seems to be involved in the adverse biological activity of PM and our deletion assay is very sensitive towards prooxidants, aim 2 is to determine whether antioxidant exposure may reduce the potential effect of PM on the frequency of deletions. The results obtained in this project could reinforce the notion that PM act through generation of oxidative stress and potentially, after similar studies have been carried out in humans, could lead to the recommendation of taking nutritional antioxidants by occupationally PM exposed workers. This research will be done primarily in Mexico at Universidad Nacional Autonoma de Mexico and the Institute Nacional de Cancerologia in collaboration with Alvaro R. Osornio Vargas and Claudia Garcia Cuellar as an extension of NIH grant #R01 ES09519.

墨西哥城是超过1800万人的家园，他们呼吸着北美污染最严重的空气。 空气污染中含有的颗粒物（PM）包括数量惊人的已知致癌物质， 有一些流行病学的迹象表明，暴露于PM会导致人类癌症。我们已经展示了在 初步结果表明，暴露于柴油机废气颗粒显着增加DNA的频率， 小鼠中的缺失。遗传不稳定性，特别是DNA缺失与癌症的病因学有关。在 此外，许多其他致癌物也诱导这种缺失，其中有几种是通过氧化机制。 目的1是确定来自墨西哥城不同地区的PM是否会增加DNA的频率， 小鼠中的缺失。这一发现可能揭示PM与 暴露和癌症，这是目前未知的。由于氧化应激似乎参与了 PM的生物活性和我们的缺失测定对促氧化剂非常敏感，目的2是确定 抗氧化剂暴露是否可以降低PM对缺失频率的潜在影响。结果 在这个项目中获得的结果可以加强PM通过产生氧化应激而起作用的概念， 在对人类进行类似的研究后，可能会建议服用 营养抗氧化剂的职业PM暴露工人。 这项研究将主要在墨西哥国立自治大学和 国家癌症研究所与Alvaro R.奥索尼奥·巴尔加斯和克劳迪娅·加西亚 Cuellar作为NIH资助#R01 ES09519的扩展。