HUMAN PERIPHERAL BLOOD STUDIES OF MUTATIONS IN THE ABERJONA REGION

阿伯霍纳地区的人类外周血突变研究

• 批准号: 6106147
• 负责人: William G Thilly
• 金额: $ 17.53万
• 依托单位: MASSACHUSETTS INSTITUTE OF TECHNOLOGY
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-04-01 至 2001-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6106147
• 关键词: arsenic; child (0-11); chromium; environmental toxicology; fresh water environment; gene mutation; genetic markers; hazardous substances; heavy metals; human subject; industrial waste; mutagens; ribosomal RNA; water pollution

Description: The chemical analysis of sediment cores in the peat marsh near municipal wells G and H confirmed by similar analysis in the Upper Mystic Lake indicates that a massive bolus of heavy metals including chromium and arsenic passed by the well sites sometime after the early 1960's. Hydrogeologic models show that some 60% of the water drawn from wells G and H water drawn in the summers of 1964 to 1979 had to come from the Aberjona River. Based on the sedimentary record estimated flow rates and modelling of local conditions, it is calculated that chromium and arsenic concentrations of 200 mug/L and 50 mug/L respectively were present in the drinking water of East Woburn. This is equivalent to 4muM chromate which was found to be markedly mutagenic to human cells in a 5 hour exposure. The mutational spectrum of this treatment has been determined in exon 3 of the human hprt gene in vitro. It is now proposed to study the mutational spectra in blood cells sampled from residents of East Woburn, West Woburn, Arlington and West Medford to discover if the genetic effects of chromium may be found in exposed residents. Before this, it is proposed that samples of childhood hair be collected for analysis to discover if and when exposure occurred. Given confirmatory results, they will use their community outreach effort to explain the goals, methods and limitations of their technology. They propose to enroll five multi-generational families who collectively represent persons of both genders, a wide distribution of ages and European and African ancestry. In particular two families living primarily in East Woburn 1960-1990 will be sought whose source of drinking water was the municipal water supply. In parallel with this public education and solicitation effort they propose to pursue certain additional technical goals which are needed for facile and accurate mutational spectrometry in human blood samples. These involve improved methods for sample preparation, exploration of certain multicopy nuclear DNA sequences for suitability, development of internal standards and development of laboratory protocols to assure quality, accuracy and donor confidentiality. Initially they propose to obtain some fifty mutational spectra from fifty donors. They hope to be able to discern if the mutational spectrum of chromate is present in the DNA samples of persons who consistently drank water from wells G and H and not present in unexposed individuals. They then hope to see if there are differences among spectra within families on the basis of age or gender; they then hope to be able to discover if there are significant differences within or among families in our studies. If successful, they will have laid the basis for a new and valuable way to discover the amount and kinds of mutations in human populations and offer the means to identify environmental causes, if any, of genetic change in humans.

描述：泥炭沼泽沉积物岩心的化学分析 在市政威尔斯G井和H井附近， 神秘湖表明，大量的重金属， 铬和砷通过井场后的某个时候， 六十年代水文地质模型显示，约60%的水来自 从1964年到1979年夏天抽取的威尔斯G井和H井的水 从阿伯乔纳河来的根据沉积记录估算的流量 率和模拟当地条件，据计算，铬 砷浓度分别为200 μ g/L和50 μ g/L， 东沃本的饮用水中发现的这相当于 4 μ M铬酸盐，发现其对人细胞具有显著的致突变性 暴露5小时后。这种治疗的突变谱 在体外测定人hprt基因外显子3。 现在有人提议研究血细胞取样中的突变谱 来自东沃本、西沃本、阿灵顿和西梅德福的居民 为了发现铬的遗传效应是否可以在暴露的环境中发现， 居民 在此之前，有人提议收集儿童时期的头发样本 进行分析，以发现是否以及何时发生了接触。给定 确认结果后，他们将利用社区外展工作， 解释其技术的目标、方法和局限性。他们 建议招收五个多代同堂的家庭， 代表男女两性，年龄分布广泛， 欧洲和非洲血统。尤其是两个家庭 主要是在东沃本1960-1990年将寻求其来源， 饮用水是市政供水。 在进行公众教育和募捐的同时， 我建议追求某些额外的技术目标， 用于人类血液样本中的简易和准确的突变光谱分析。 这些措施包括改进样品制备方法， 某些多拷贝核DNA序列的适用性，开发 内部标准和制定实验室协议，以确保 质量、准确性和捐助者保密性。 最初，他们建议从50个突变谱中获得大约50个突变谱。 捐助者。他们希望能够辨别出， 铬酸盐存在于那些经常喝酒的人的DNA样本中， 来自威尔斯G和H井的水，未暴露个体中不存在。他们 然后希望看看家族内的光谱是否存在差异， 根据年龄或性别，他们希望能够发现， 在我们的家庭中， 问题研究 如果成功，他们将为一种新的有价值的方式奠定基础。 发现人类群体中突变的数量和种类， 提供手段，以确定环境原因，如果有的话，遗传 人类的变化。