MOLECULAR MECHANISMS OF ORGANOPHOSPHATE IMMUNOTOXICITY

免疫抑制的分子机制，由两个杂质中， 有机磷农药马拉硫磷、乙酰甲胺磷和杀螟松， O，O，S-三甲基硫代磷酸酯（OOS-TMP）和O，S，S-三甲基 二硫代磷酸酯，将被检查。 巨噬细胞，通过细胞 分离和重组实验，已被证明是 受OOS-TMP处理影响最大的淋巴样细胞。 中的阻塞 巨噬细胞的成熟，这发生在急性施用 将确定OOS-TMP。 研究将包括巨噬细胞 细胞表面标志物Ia、Mac-1、Mac-2和F4/80，功能活性和 分泌产物 结构类似物OSS-TMP的抑制作用 对细胞溶解效应器功能的影响将使用 功能上确定的细胞毒性T淋巴细胞（CTL）和其他细胞溶解性T淋巴细胞（CTL）， 效应细胞 阻断鼠CTL功能的位点将是 使用缀合物形成和Ca 2+脉冲技术测定。 的 将使用放射性标记的OSS-TMP鉴定分子位点， 生化分析 此外，还改进了比色测定法， (dye将研究其适用性 作为细胞毒性和细胞抑制活性的筛选试验， 环境毒物 该测定可作为标准品的替代品 台盼蓝排除法用于评估细胞活力。

The molecular mechanisms of immune suppression by two impurities in the organosphosphate pesticides, malathion, acephate and fenitrothion, O,O,S-trimethyl phosphorothioate (OOS-TMP) and O,S,S-trimethyl phosphorodithioate, will be examined. Macrophaages, through cell separation and reconstitution experiments, have been shown to be the lymphoid cell most affected by OOS-TMP treatment. The blockage in the maturation of macrophages which occurs following acute administration of OOS-TMP will be identified. Studies will include changes in macrophage cell surface markers, Ia, Mac-1, Mac-2 and F4/80, functional activity and secretory products. The inhibitory effect of a structural analog OSS-TMP on cytolytic effector function will be examined in detail using functionally defined cytotoxic T lymphocytes (CTL) and other cytolytic effector cells. The site(s) of the blockade of murine CTL function will be determined using conjugate formation and Ca2+ pulse techniques. The molecular sites will be identified using radiolabelled OSS-TMP and biochemical analyses. In addition, an adaptation of a colorimetric assay (dye reduction) for cell viability will be investigated for its suitability as a screening assay for the cytotoxic and cytostatic activities of environmental toxicants. This assay may be an alternative to the standard trypan blue exclusion method for assessing cell viability.