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: 5211110
• 负责人: WILLIAM G THILLY
• 金额: --
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/5211110
• 关键词: arsenic; child (0-11); chromium; environmental toxicology; fresh water environment; gene mutation; genetic markers; 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：泥炭沼泽中沉积物芯的化学分析 靠近市政井的G和H，通过在上部的类似分析中证实 神秘湖表明，大量的重金属大量 早期的某个时候，铬和砷在井站经过 1960年代。水文地质模型表明，大约60％的水 在1964年至1979年的夏季，Wells G和H的水必须来 来自阿伯乔纳河。根据沉积记录估计流量 当地条件的速率和建模，据计算铬 和砷浓度分别为200 mug/L和50杯/L 出现在东沃本的饮用水中。这等同于 4mum铬酸盐，发现对人类细胞显着诱变 在5小时的曝光中。这种治疗的突变范围具有 在体外人类HPRT基因的外显子3中确定。 现在建议研究采样的血细胞中的突变光谱 来自East Woburn，West Woburn，Arlington和West Medford的居民 发现是否在暴露中发现铬的遗传作用 居民。 在此之前，建议收集儿童头发的样品 为了分析，可以发现是否发生暴露和何时发生。给出 确认结果，他们将利用社区外展工作来 解释其技术的目标，方法和局限性。他们 建议注册五个共同的多代家庭 代表两种性别的人，年龄的广泛分布和 欧洲和非洲血统。特别是两个家庭 主要是在东沃本（East Woburn）1960 - 1990年。 饮用水是市政供水。 与他们的公共教育和招生努力并行 建议追求某些需要的其他技术目标 用于人类血液样本中的简便而准确的突变光谱法。 这些涉及改进的样品制备方法，探索 某些多拷贝核DNA序列适合性，发展 内部标准和制定实验室协议以确保 质量，准确性和捐助者机密性。 最初，他们建议从五十个获得大约五十个突变光谱 捐助者。他们希望能够辨别出是否的突变频谱 铬酸盐存在于持续喝的人的DNA样本中 来自Wells G和H的水，不存在于未暴露的个体中。他们 然后希望看看家庭内部光谱之间是否存在差异 根据年龄或性别；然后，他们希望能够发现是否 我们的家庭或家庭之间存在显着差异 研究。 如果成功，他们将为一种新的和宝贵的方式奠定基础 发现人类人群中的突变数量和种类 提供识别遗传原因（如果有的话）的手段 人类的变化。