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TP2 Metals in the Environment: Regulatory and Risk Concerns
(BAS-1125-067990) Modulation of gene expression in the spleen of Peromyscus and Rats exposed to lead.
Basu, A1, Showe, L2, Nebozhyn, M2, Spotila, J1, 1 Environmental Science Program, Dept. of Bioscience and Biotechnology, Drexel University, Philadelphia2 Microarray Facility, The Wistar Institute, Philadelphia
ABSTRACT- The toxic metal lead (Pb++) is a widespread environmental health hazard as well as a special concern for the US Army, which extensively utilizes lead in ammunition. We have employed cDNA microarrays to analyze the effects of acute Pb++- exposure on gene expression patterns in deer mice (Peromyscus maniculatus<\i>), a widely available wild rodent in North America, and laboratory rats (Rattus rattus<\i>). In deer mice we identified novel putative targets of Pb++-mediated toxicity in spleen in the laboratory, including several genes belonging to the metabolic and transport pathways of acetyl-CoA, an important metabolic component in the mitochondrial section of intermediate metabolism. The imbalance in Acetyl-CoA metabolism may limit production of succinyl-CoA, one of the two reactants necessary for the synthesis of -aminolevulenic acid. Lead toxicity is known to inhibit the synthesis of -aminolevulenic acid, a precursor of heme, which leads to anemia. We also determined gene modulation in the spleens of Peromyscus maniculatus<\i> collected from contaminated sites on an Army ammunition plant. Expression of some genes was enhanced and expression of other genes was depressed. We also measured gene expression in laboratory rats, a model organism which has been the subject of many lead toxicity studies. We compared gene expression data with the blood-Pb level of individual mice and rats. This allowed us to identify a set of putative target genes modulated in Peromyscus maniculatus<\i> and laboratory rats due to lead exposure. These data will allow us to create a gene expression database on an environmental toxicant.
Key words: Lead toxicity, gene expression, rodents
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