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

描述：该项目的主要目标是确定遗传 木材现场提取物中复杂化学混合物的毒性 作为其潜力的指标 致癌性将在小鼠模型中测试田间浸提液， 一种新的诱导DNA损伤的体外系统（共价DNA 加合物），将通过32 P-标记后测定进行评估。的 研究人员建议（1）产生提取物和组织特异性PAH- DNA加合物特征和水平作为遗传毒性终点，（2）确定 来源的主要PAH-DNA加合物诱导的领域提取物，（3）显示 多氯酚是否诱导氧化应激相关的大体积 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 田间化学品间协同或拮抗作用 体内提取物，（6）检查现场提取物是否引起减少 小鼠模型中肝脏I-化合物水平，和（7）测试是否， 在不存在代谢活化的情况下， 样品诱导提取物特异性DNA加合物的体外特征和水平 以及这种特性是否代表了 含水垃圾场流出物。这些研究旨在提供 木材防腐剂毒性的定性和定量数据， 一个细胞的遗传物质。

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.