TOXICOLOGICAL SIGNIFICANCE OF PESTICIDE METABOLISM

这项提案的总体目标是提供信息 这将有助于确定在哪些情况下 个体可能异常地易受(或抵抗) 杀虫剂的毒性行为。该项目将重点放在 有机磷杀虫剂，因为它们代表主要类别 作为杀虫剂使用的化学物质，由于它们具有潜在的 对人体的严重毒害。研究将被定向 关于影响哺乳动物的那些因素的特征 有机磷杀虫剂As的生物转化反应 以及这种反应的后果。预计 这些研究将提供有用的资料，以评估 有机磷杀虫剂及其对健康的危害 可能与某些其他外来物质产生有毒的相互作用 化学制品。此外，这项拟议的研究将有助于 有关新陈代谢系统的基础知识 这些杀虫剂的生物转化。其中的具体目标 本研究的主要内容如下：1)继续调查 某些特定物质肝外激活的毒理学意义 有机硫磷杀虫剂。2)调查原因 多种谷胱甘肽依赖的解毒作用 二甲基取代有机磷杀虫剂在体外发生 但不是在体内。3)确定和描述以下因素 影响肝脏和血清A-酯酶活性。包括在此 目标将是研究动力学和物理化学 “高活动”与“低活动”形式的区别 人血清A-酯酶。4)对两者进行生化表征 从小鼠肝微粒体中纯化的A-酯酶的形态 实验室。5)确定影响分泌物的因素 肝脏中的A-酯酶(S)。这些研究还将重点放在 分泌型(S)与分泌型A-酯酶(S)的比较 在肝微粒体中发现的各种形式。

The overall objective of this proposal is to provide information which will aid in the identification of conditions in which individuals might be unusually susceptible (or resistant) to the toxic actions of pesticides. The project will focus on the organophosphorus insecticides since they represent the major class of chemicals used as insecticides, and since they have potential for serious toxic effects in humans. Research will be directed towards characterizing those factors which affect the mammalian biotransformation reactions of organophosphorus insecticides, as well as the consequences of such reactions. It is expected that these studies will provide information useful in assessing the health hazards of organophosphorus insecticides, as well as their potential for toxic interactions with certain other foreign chemicals. Additionally this proposed research will contribute to the fundamental knowledge of those metabolic systems involved in the biotransformation of these insecticides. The specific aims in this research are as follows: 1) To continue to investigate the toxicological significance of extrahepatic activation of certain organothiophosphorus insecticides. 2) To investigate why glutathione-dependent detoxification of numerous dimethyl-substituted organophosphorus insecticides occurs in vitro but not in vivo. 3) To identify and characterize factors which affect hepatic and serum A-esterase activities. Included in this aim will be the investigation of kinetic and physiochemical differences between "high activity" and "low activity" forms of human serum A-esterase. 4) To characterize biochemically the two forms of A-esterase purified from mouse hepatic microsomes in this laboratory. 5) To characterize the factors affecting secretion of A-esterase(s) from liver. These studies will also focus on comparisons of the secreted form(s) of A-esterase(s) with those forms found in hepatic microsomes.