Heavy metals such as lead (Pb) represent a major category of contaminants at Superfund sites. Pb has been demonstrated to cause neurological toxicity, behavioral deficits and immunotoxicity. Given the value of effective immune function, it is important to identify risk factors that may influence susceptibility to immunotoxicity. Possible risk modifiers include age and diet, both of which can affect immune status and may, therefore, alter susceptibility to Pb-induced immunotoxicity. In addition, therapeutic measures such as chelation, designed to modify the bioavailability of Pb in vivo, may alter the outcome of Pb exposure. During embryonic development, toxicant exposure may interfere with growth and differentiation, resulting in persistent abnormalities. The neurological effects of embryonic exposure have been described, but less is known about immunotoxic effects as a result of embryonic Pb exposure. Developmental immunotoxicity of Pb may not correlate with that of postnatal exposure, since immune function during development is quite distinct from that of the homeostatic immune system. This project will assess immune function in young animals following embryonic Pb exposure. Results will be obtained from two species (pregnant rat model and in ovo chicken model), thereby increasing possible applicability to other species. A panel of immune assessment assays will be utilized, including in vivo and in vitro measurements. Dietary intake and immune function are tightly linked. One dietary component which is associated with significant immunomodulation and which varies in populations exposed to Pb is protein, both quantity and quality (i.e., amino acid content). Decreases in protein intake have also been shown to amplify Pb retention and subsequent toxicity to other physiological systems. The interactions between altered immune function and altered Pb metabolism as a result of dietary changes could provide useful mechanistic information; in addition, dietary intake in exposed individuals may have predictive and/or therapeutic value. This proposal examines the effect of alterations in dietary protein (quantity and specific amino acid intake) on Pb-induced immunotoxicity in the rat. Chelation, in vivo control of Pb bioavailability, is a primary therapeutic measure for Pb exposure. Dimercaptosuccinate (DMSA), a chelator to be utilized in a proposal regarding rat neurobehavior (Project under Drs. Strupp and Levitski), will be administered to the pregnant rats to examine the abrogation of maternal vs. embryonic Pb- induced immunotoxicity. Results of these two projects will furnish information on DMSA protection of multiple target systems in similar embryonic models by controlling in vivo availability. The proposed research should provide a solid foundation of information regarding the immunotoxic effects of embryonic Pb exposure and the interaction of factors which may modify that immunotoxicity.
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