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PT14 Toxicity of Mixtures
(PT219) Pb accumulation and biomarker responses in deer mice (Peromyscus maniculatus) dosed with Pb, Cu, and Zn in drinking water.
McBride, T1, McFarland, C1, Wu, H1, Hooper, M1, 1 Texas Tech University, Lubbock, TX, USA
ABSTRACT- Studies of mixed metal (Cd, Cu, Pb, Zn) exposure in deer mice (Peromyscus maniculatus)at the Anaconda Smelter Site, Montana, have demonstrated that blood Pb levels that lead to erythrocyte -aminolevulinic acid dehydratase (ALAD) inhibition in lab rodent species, do not result in similar inhibition in these field-exposed wild rodents. The effects of Pb exposure on tissue Pb accumulation and heme synthesis pathway and oxidative stress biomarkers in adult deer mice were examined to better understand Pb accumulation and effects in the field. Though deer mice are regularly utilized as monitors for metal exposure in contaminated settings, few controlled dosing studies have been performed investigating biomarker responses to metal, and particularly Pb, exposure. We dosed adult deer mice for 21 days with Pb acetate at 0, 0.1, 1, 10, 100, and 1000 g/ml (nominal concentration; N = 6-11/dose) in drinking water, resulting in a mean daily doses of approximately 0, 0.03, 0.3, 3.0, 30, and 300 mg Pb/kg body weight/day. Tissues demonstrated dose-dependent Pb accumulation, with significant elevations above control in the 10, 100 and 1000 ppm groups in blood (2.5, 19, 66 g/dl), hepatic (0.34, 1.0, 6.1 ppm wet wt.) and renal tissues (0.57, 3.2, 25 ppm w.w.), respectively. ALAD activity was inhibited approximately 20, 50, and 80% at the 10, 100, and 1000 ppm dose levels, respectively, as has been seen in standard laboratory rodent species. Additional studies will be presented where we examined Cu and Zn exposures, concurrent with effect-inducing Pb exposure, to assess the role these co-occurring metals play in diminishing biomarker response. Additional oxidative stress and heme synthesis endpoints will be presented for comparison with ALAD inhibition. Data presented will be useful for interpreting Pb exposure and effect findings in field assessments of wild rodents on mixed metal-contaminated sites. Sponsored by NIEHS P42ES04696.
Key words: metal mixture, peromyscus maniculatus, biomarkers, deer mouse
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