ORGANIC MERCURY TOXICITY AT CHROMOSOMAL LEVELS

染色体水平的有机汞毒性

• 批准号: 3251139
• 负责人: DIETER W GRUENWEDEL
• 金额: $ 11.57万
• 依托单位: UNIVERSITY OF CALIFORNIA AT DAVIS
• 依托单位国家: 美国
• 财政年份: 1986
• 资助国家: 美国
• 起止时间: 1986-05-01 至 1989-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3251139
• 关键词: DNA; HeLa cells; chromatin; chromosomes; circular dichroism; gel electrophoresis; genetic transcription; mercury poisoning; messenger RNA; metallothionein; methylmercury; nucleosomes; organic chemicals; teratogens

The effect of the environmental pollutant and toxicant methylmercury on chromosome structure and function will be studied in cells of the continuous human cell line HeLa S3 (1) by analyzing, subsequent to methylmercury treatment, the fine structure as well as transcriptional activity of the cells' dispersed form of interphase nuclei (chromatin) with the aid of 'mapping' techniques (two-dimensional gel electrophoresis); (2) by monitoring the activity of the heavy metal-inducible metallothionein genes based on their capability to produce metallothionein mRNAs as well as metallothionein; and (3) by studying, in an extracellular system, the physico-chemical properties of nucleosomes, reassembled from the constituent chromosomal histone and non-histone proteins and DNA in the presence and absence of methylmercury, with the aid of thermal denaturation and circular dichroism measurements. It is the ultimate aim of this plan to provide, at the molecular level, a rationale for the finding that organomercurials in general, and methylmercury in particular, are powerful in vivo clastogens and teratogens (in addition to their also being powerful neurotoxicants).

环境污染物和有毒物质甲基汞对 染色体结构和功能将在细胞中进行研究， 连续人细胞系HeLa S3 (1)通过分析甲基汞处理后的精细结构， 以及细胞分散形式的转录活性， 间期核（染色质）与“映射”技术的帮助 （二维凝胶电泳）; (2)通过监测重金属诱导的金属硫蛋白的活性 基因基于它们产生金属硫蛋白mRNA的能力，以及 金属硫蛋白;和 (3)通过研究细胞外系统中 核小体的性质，从组成染色体 组蛋白和非组蛋白蛋白和DNA在存在和不存在 甲基汞，借助于热变性和圆二色性 测量. 该计划的最终目标是在分子水平上提供一个 一般来说，有机汞制剂 尤其是甲基汞，是体内强有力的致染色体断裂剂和致畸剂 (in此外，它们也是强大的神经毒素）。