32P-POSTLABELING BASED BIOASSAY OF TOXIC CHEMICALS IN WASTE DUMPSITES

基于 32P-后标记的垃圾填埋场中有毒化学品的生物测定

• 批准号: 6106229
• 负责人: KURT RANDERATH
• 金额: $ 11.82万
• 依托单位: TEXAS A&M UNIVERSITY HEALTH SCIENCE CTR
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-04-05 至 2000-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6106229
• 关键词: DNA; DNA damage; adduct; bioassay; biomarker; carbopolycyclic compound; carcinogen testing; chemical carcinogenesis; dioxins; environmental contamination; environmental toxicology; halobiphenyl /halotriphenyl compound; halohydrocarbon; human genetic material tag; human tissue; industrial waste; laboratory mouse; laboratory rat; liver cells; lymphocyte; occupational hazard; skin; tissue /cell culture; toxicant interaction; toxicant screening

Description: The major goal of this project is to determine the genetic toxicity of complex chemical mixtures present in field extracts from wood preserving and oily waste sites as an indicator of their potential carcinogenicity. Field extracts will be tested in a mouse model and by a novel in vitro system for the induction of DNA damage (covalent DNA adducts), which will be assessed by the 32P-postlabeling assay. The investigators propose to (1) produce extract- and tissue-specific PAH- DNA adduct profiles and levels as genotoxic endpoints, (2) identify the sources of major PAH-DNA adducts induced by field extracts, (3) show whether polychlorinated phenols induce oxidative stress-associated bulky DNA lesions, (4) determine the relationships between genotoxic potencies of field extracts and tumor initiating activities, (5) assess possible synergistic or antagonistic interactions between chemicals in field extracts in vivo, (6) examine whether field extracts elicit reductions of hepatic I-compound levels in the mouse model, and (7) test whether, in the absence of metabolic activation, aqueous extracts of field samples induce extract-specific DNA adduct profiles and levels in vitro and whether this property represents an indicator of genotoxicity of aqueous dumpsite effluents. These studies are designed to provide qualitative and quantitative data on the toxicity of wood preserving and oily waste sites to the genetic material of a cell.

描述：该项目的主要目标是确定遗传 木材现场提取物中存在的复杂化学混合物的毒性 保护和含油废物场作为其潜力的指标 致癌性。现场提取物将在小鼠模型中进行测试 一种诱导 DNA 损伤的新型体外系统（共价 DNA 加合物），将通过 32P 标记后测定进行评估。这 研究人员建议 (1) 生产提取物和组织特异性的 PAH- DNA 加合物谱和水平作为基因毒性终点，(2) 确定 现场提取物诱导的主要 PAH-DNA 加合物的来源，(3) 显示 多氯酚是否会诱导氧化应激相关的体积增大 DNA 损伤，(4) 确定遗传毒性效力之间的关系 现场提取物和肿瘤引发活性，（5）评估可能的 现场化学品之间的协同或拮抗相互作用 体内提取物，（6）检查现场提取物是否引起减少 小鼠模型中肝 I-化合物水平的变化，以及 (7) 测试是否， 在没有代谢活化的情况下，田野的水提取物 样品在体外诱导提取物特异性 DNA 加合物谱和水平 以及该特性是否代表遗传毒性的指标 垃圾场废水。这些研究旨在提供 有关木材防腐剂毒性的定性和定量数据 油性废物是细胞遗传物质的场所。