MOLECULAR MECHANISMS OF ORGANOPHOSPHATE IMMUNOTOXICITY

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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.