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; 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 来自木材的田间提取物中的复杂化学混合物的毒性 保存和油性废物站点作为其潜力的指标 致癌性。现场提取物将在鼠标模型和通过 一种用于诱导DNA损伤的新型体外系统（共价DNA 加合物），将通过32p固定标签测定法进行评估。这 研究人员提议（1）产生提取物和组织特异性PAH- DNA加合谱和水平作为遗传毒性终点，（2）确定 由现场提取物诱导的主要PAH-DNA加合物的来源，（3）显示 多氯苯酚是否诱导氧化应激相关的笨重 DNA病变，（4）确定遗传毒性效力之间的关系 （5）评估现场提取和肿瘤发起活动 化学物质之间的协同或拮抗相互作用 在体内提取物，（6）检查现场提取是否引起降低 鼠标模型中的肝I-复合水平，（7）测试是否 在没有代谢激活的情况下，田间水提取物 样品在体外诱导提取物特异性DNA加合物曲线和水平 以及该特性是否代表了遗传毒性的指标 水垃圾场废水。这些研究旨在提供 关于保存木材毒性的定性和定量数据 油性废物位置到细胞的遗传物质。