INHIBITION OF PARAQUAT OXYGEN-MEDIATED TOXICITY

提出了亚甲蓝和硫代素对百草枯的影响。 以大鼠为实验模型进行毒性研究。百草枯 通过氧自由基的产生，NADPH的耗竭， 和混合二硫化物生产。亚甲蓝和硫代素是已知的 刺激NADPH的产生，初步实验表明，它们将 取代氧作为电子载体，并与氧自由基反应。 通过取代氧作为电子载体，亚甲基蓝和硫化物 应防止氧或百草枯自由基的形成。上一首 减少百草枯毒性的尝试使用的药剂通过去除 在他们形成之后的激进分子。来自此项目的信息 也将被用于调查其他环境毒素(铅， 芳香族硝酸盐溶剂)可能产生氧自由基的速度较慢 费率。 首席调查员对从事环境保护工作感兴趣。 毒理学，重点研究抗氧化剂的生化变化 来自环境化学物质的酶系统。上述项目将使 研究定义明确的氧自由基产生系统的调查者 以及与抗氧化酶系统的相互作用。通过引入一种改变 在体系(亚甲基蓝或硫代)中，原始贡献 科学知识也可以被创造出来。该奖项将使 调查员致力于环境毒理学(80%的研究， 20%的临床或教学)，取消所有其他职责或责任。 加州大学圣地亚哥分校拥有出色的研究和临床经验 环境毒理学研究设施。有一家诊所 加州大学旧金山分校职业健康小组 圣地亚哥--圣地亚哥医学中心和环境毒理学项目 迭戈动物园。此外，该大学距离墨西哥很近 为美国没有发现的环境问题提供独特的风险敞口 各州。首席调查员将能够参与这两项 上述方案。预计首席调查员， 完成课程后，将加入病理学系 在加州大学圣地亚哥分校担任助理教授 环境方面的研究、教学和临床责任 毒物学。

It is proposed that the effects of methylene blue and thionin on paraquat toxicity be investigated using rats as the experimental model. Paraquat produces its toxic effects by oxygen-radical production, NADPH depletion, and mixed disulfide production. Methylene blue and thionin are known to stimulate NADPH production and preliminary experiments show they will replace oxygen as electron carriers and also react with oxygen radicals. By replacing oxygen as the electron carrier, methylene blue and thionin should prevent the formation of oxygen or paraquat radicals. Previous attempts to reduce paraquat toxicity used agents that worked by removing the radicals after their formation. Information derived from this project would also be used to investigate other environmental toxins (lead, aromatic-nitrate solvents) that may produce oxygen radicals at a slower rate. The principal investigator is interested in a career in environmental toxicology with research emphasis on biochemical changes in anti-oxidant enzyme systems from environmental chemicals. The above project will enable the investigator to study a well defined oxygen-radical producing system and interaction with anti-oxidant enzyme systems. By introducing a change in the system (methylene blue or thionin) an original contribution to scientific knowledge may also be made. The award would enable the investigator to devote full time to environmental toxicology (80% research, 20% clinical or teaching) by removing all other duties or responsibilities. The University of California, San Diego has excellent research and clinical facilities for studying environmental toxicology. There is a clinical occupational health group at the University of California, San Diego-Medical Center and an environmental toxicology program at the San Diego Zoo. In addition, the University's close proximity to Mexico provides unique exposure to environmental problems not found in the United States. The principal investigator will be able to participate in both of the above programs. It is anticipated that the principal investigator, following completion of the program, will join the Department of Pathology at the University of California, San Diego as an Assistant Professor with research, teaching, and clinical responsibilities in environmental toxicology.