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

描述：这个项目的主要目标是确定基因 木材田间萃取物中复杂化学混合物的毒性 保存和油污废物场地作为其潜力的指标 致癌性。田野提取物将在小鼠模型中进行测试，并通过 一种新的诱导DNA损伤的体外体系(共价DNA 加合物)，这将通过32P-后标记试验进行评估。这个 研究人员建议(1)产生提取物和组织特异性多环芳烃- DNA加合物图谱和水平作为遗传毒性终点，(2)识别 田间提取液诱导的主要多环芳烃-DNA加合物的来源，(3)显示 多氯酚是否会导致氧化应激相关的大量物质 DNA损伤，(4)确定基因毒性效力之间的关系 田野提取物和肿瘤启动活性，(5)评估可能 田间药剂间的协同或拮抗作用 活体提取物，(6)检查田间提取物是否会引起减量 小鼠模型中肝脏I-化合物水平的变化，以及(7)测试是否， 在没有代谢激活的情况下，大田水提物 样品在体外诱导提取液特异的DNA加合物图谱和水平 以及这一特性是否代表了一种遗传毒性指标 含水的垃圾场流出物。这些研究旨在提供 木材防腐防腐毒性的定性和定量数据 油性废物部位到细胞的遗传物质。

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.