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Immunological and biochemical responses in mice treated with mercuric chloride
Authors:M P Dieter  M I Luster  G A Boorman  C W Jameson  J H Dean  J W Cox
Affiliation:1. National Institute of Environmental Health Sciences, P.O. Box 12233, Research Triangle Park, North Carolina 27709, USA;2. Chemical Industry Institute of Toxicology, P.O. Box 12137, Research Triangle Park, North Carolina 27709, USA;3. Midwest Research Institute, 425 Volker Blvd., Kansas City, Missouri 64110 USA
Abstract:Adult B6C3F1 male mice were given water containing 3, 15, and 75 ppm mercury (as mercuric chloride) for 7 weeks. There were dose-related increases in blood and kidney mercury levels but only the former showed a time-dependent change. Mercury was not detected in any of the lymphoid organs except for the spleen. There was no mortality and only minimal histological changes occurred in kidneys of dosed mice. Nonspecific toxicity occurred at the 75 ppm dose level, consisting of small differences in body and organ weights, hematological changes, and general enzyme inhibition in the bone marrow and spleen. However, there were specific immunotoxic and biochemical alterations in lymphoid organs of mice treated at the lower doses of mercury. The immunological defects were consistent with altered T-cell function as evidenced by decreases in both T-cell mitogen and mixed leukocyte responses. There was a particular association between the T-cell defects and inhibition of thymic pyruvate kinase, the rate-limiting enzyme for glycolysis. The differences in the pattern of enzyme responses among lymphoid organs implied that two mechanisms of mercury toxicity were operative--one at high concentrations that caused physicochemical enzyme inhibition and another at low concentrations that caused indirect enzyme inhibition.
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