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Final Progress Reports: University of Arizona: Research Support Core

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Superfund Research Program

Research Support Core

Project Leader: Jon Chorover
Grant Number: P42ES004940
Funding Period: 2000-2015
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Final Progress Reports

Year:   2014  2009  2004 

The Analytical Section of the Hazard Identification Core was critical to the Superfund Program.  Since many of the research projects performed are studying metals (arsenic), the ICP mass spectrometer was extensively used for both total metal analysis and for chemical speciation (e.g. arsenite, arsenate, monomethyl As(III), etc).  Over 9,000 ICP-MS analyses were performed that resulted in the facilitating research aims in seven of the UA-Superfund research projects and their associated publications.

For Toxicity Evaluation of degradation products from remediation studies for the environmental engineers and scientists, this Core developed cytotoxicity studies in HepG2 (human) and H4IIE (rat) cells which included LDH leakage and MTT analyses. Initial plans were to have gene array analyses available for toxicity screening but this approach proved to be too costly and time consuming to be practical. Genotoxicity analyses were available with the Ames bacterial mutagenesis assay found to be the most useful and reproducible.

Human Studies - Dr. Klimecki from the Arizona Respiratory Sciences Center studied genetic polymorphism in genes involved in arsenic biotransformation this past year. The recent characterization of specifically defined, arsenic metabolism genes has sparked genetic association studies aimed at relating the genetic makeup of arsenic-exposed humans to their urinary arsenic metabolic profile, and ultimately to human toxicity/carcinogenicity. A necessary prerequisite to adequately conduct these genetic association studies is a catalog of commonly occurring genetic polymorphisms in critical genes involved in arsenic metabolism. Dr. Klimecki has catalogued two arsenic metabolism genes, glutathione-S-transferase omega (GSTO-1) and nucleoside phosphorylase (NP), for commonly occurring polymorphisms. Individuals from defined groups of European ancestry and Indigenous American ancestry were profiled. A dramatic lack of genetic variation was observed in the Indigenous American population for GSTO-1, while this group was substantially more polymorphic for NP. These results suggest that ethnicity may play a role in the genetic predisposition for arsenic metabolism. The significance of these discoveries is that they can be expected to lead to the identification of individuals who are hypersensitive to arsenic toxicity and therefore must be protected from arsenic exposure.

The critical importance of the Hazard Identification Core is the presence of a centralized site for biological and chemical analyses that serve virtually every one of the Research Projects - both biomedical investigations as well as the environmental sciences/engineering studies. This Core allows rapid identification of intermediates generated biologically or chemically allowing their scientists/engineers to quickly understand the nature of the products made as well has their potential toxicity.

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