Grantee Research Project Results

2008 Progress Report: Biomarkers Of Health Risks Associated With Environmental Exposure To Arsenic

EPA Grant Number: R832735
Title: Biomarkers Of Health Risks Associated With Environmental Exposure To Arsenic
Investigators: Stýblo, Miroslav , García-Vargas, Gonzalo G , Del Razo, Luz M.
Current Investigators: Stýblo, Miroslav , García-Vargas, Gonzalo G , Del Razo, Luz M. , Loomis, Dana , Ethan, Lange , Drobna, Zuzana
Institution: University of North Carolina at Chapel Hill
Current Institution: University of North Carolina at Chapel Hill , University of Nevada - Reno
EPA Project Officer: Callan, Richard
Project Period: February 13, 2006 through February 12, 2009 (Extended to February 12, 2010)
Project Period Covered by this Report: February 13, 2008 through February 12,2009
Project Amount: $749,988
RFA: Early Indicators of Environmentally Induced Disease (2004) RFA Text | Recipients Lists
Research Category: Human Health

Objective:

To examine interindividual variations in urinary profiles of methylarsonite (MAs^III) and dimethylarsinite (DMAs^III), the toxic metabolites of arsenic (As), in individuals exposed to inorganic As (iAs) in drinking water.
To characterize the relationship between the urinary levels of MAs^III and DNAs^III and markers of carcinogenic and diabetogenic effects of iAs.
To examine the role of genetic polymorphism for arsenic (+3 oxidation state) methyltransferase (AS3MT) in modulation of the metabolism and adverse health effects of iAs.
To study the genotype-phenotype relationship using recombinant genetic variants of AS3MT.

Progress Summary:

The main part of this project is a population-based study carried out in two arseniasis endemic areas of Mexico: Zimapan and Lagunera regions. We have completed medical examination, including skin lesion evaluation and oral glucose tolerance test, and sample collection from all study subjects (149 in Zimapan and 113 in Lagunera). All scheduled sample analyses have also been completed, including analyses of total and speciated arsenic in urines, transforming growth factor-α (TGF-α) in exfoliated bladder epithelial cells, glucose and insulin concentrations in blood, and analysis of genotypes for arsenic (+3 oxidation state) methyltransferase (AS3MT). Because of an unexpected delay in sample analyses, we received approval for a one-year no-cost extension for our project. The extension will provide sufficient time for analysis of a large amount of data collected in both study areas over a period of 3 years. Priorities for the data analysis have been established, focusing on the associations between the urinary profiles of arsenic metabolites, AS3MT polymorphisms, skin lesions, TGF-α concentration in exfoliated bladder epithelial cells, and the markers of impaired glucose tolerance and insulin resistance.

Future Activities:

The single goal of the last year on the project is to analyze the data collected in the population study in Mexico. Priorities for the data analysis have been established, focusing on the associations between the urinary profiles of As metabolites, AS3MT polymorphisms, skin lesions, TGF-α concentration in exfoliated bladder epithelial cells, and the markers of impaired glucose tolerance and insulin resistance. We expect that the statistical evaluation of these associations will be completed by the end of this year.

Journal Articles on this Report : 3 Displayed | Download in RIS Format

Publications Views
Other project views:	All 19 publications	9 publications in selected types	All 9 journal articles

Publications
Type	Citation	Project	Document Sources
Journal Article	Hernandez-Zavala A, Valenzuela OL, Matousek T, Drobna Z, Dedina J, Garcia-Vargas GG, Thomas DJ, Del Razo LM, Styblo M. Speciation of arsenic in exfoliated urinary bladder epithelial cells from individuals exposed to arsenic in drinking water. Environmental Health Perspectives 2008;116(12):1656-1660.	R832735 (2007) R832735 (2008) R832735 (Final)	Full-text from PubMed Abstract from PubMed Associated PubMed link Full-text: Environmental Health Perspectives-Full Text HTML Exit Other: Environmental Health Perspectives-Full Text PDF Exit
Journal Article	Hernandez-Zavala A, Matousek T, Drobna Z, Paul DS, Walton F, Adair BM, Dedina J, Thomas DJ, Styblo M. Speciation analysis of arsenic in biological matrices by automated hydride generation-cryotrapping-atomic absorption spectrometry with multiple microflame quartz tube atomizer (multiatomizer). Journal of Analytical Atomic Spectrometry 2008;23(3):342-351.	R832735 (2006) R832735 (2007) R832735 (2008) R832735 (Final)	Full-text from PubMed Abstract from PubMed Associated PubMed link Abstract: JAAS-Abstract Exit
Journal Article	Hester SD, Drobna Z, Andrews DMK, Liu J, Waalkes MP, Thomas DJ, Styblo M. Expression of AS3MT alters transcriptional profiles in human urothelial cells exposed to arsenite. Human & Experimental Toxicology 2009;28(1):49-61.	R832735 (2008)	Abstract from PubMed

Supplemental Keywords:

human health, sensitive populations, dose-response, carcinogen, chemicals, toxics, metals, metalloids, trace elements, gene, epidemiology, toxicology, medicine, analytical chemistry, biochemistry, analytical, spectrometry, pollutants/toxics, water, scientific discipline, arsenic, drinking water, health risk assessment, biochemistry, water pollutants, genetics, bioavailability, biomarkers, drinking water contaminants, health effects, cancer, genotype distribution, RFA, Scientific Discipline, Water, POLLUTANTS/TOXICS, Genetics, Health Risk Assessment, Arsenic, Biochemistry, Water Pollutants, Drinking Water, health effects, biomarkers, genotype distribution, bioavailability, drinking water monitoring, cancer

Progress and Final Reports:

Original Abstract

The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Conclusions drawn by the principal investigators have not been reviewed by the Agency.