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Figure shows arsenic biotransformation pathway. |
Background
Arsenic biotransformation produces several metabolites that have differing toxic potencies, leading to speculation that individual differences in arsenic metabolism in arsenic-exposed people may underlie differences in susceptibility to arsenic-induced disease. This hypothesis has been supported by several epidemiological studies that have linked inefficient arsenic methylation with higher disease risk.
Goal
The goal of this project is to define the key determinants of individual variability in arsenic metabolism, focusing particularly on arsenic methylation efficiency as measured by the ratio of DMA(V) to MMA(V) in the urine of arsenic exposed people.
Objectives
1. To identify suitable exposed populations of people who are environmentally exposed to arsenic.
2. To characterize the exposure to arsenic in these people, relevant health and lifestyle metrics, together with their urinary arsenic metabolic profile. In addition, genetic variation in genes relevant to arsenic biotransformation will be determined.
3. Analyze these data to determine which genetic and environmental factors are the strongest determinants of altered arsenic metabolism.
Project 5 publications resulting
from research conducted under the Superfund Research Program
during the grant funding period of 2005 to present.
Contact
Walt Klimecki, DVM, Ph.D.
klimecki@pharmacy.arizona.edu
520-626-7470
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