Arsenic is a global threat to health, and one of the most commonly encountered contaminants in Superfund sites in the United States. Arsenic-exposed populations have been the focus of epidemiological studies that have found a diverse set of human diseases associated with arsenic exposure, including several forms of cancer, peripheral neuropathy, and severe peripheral vascular disease. A natural focus of epidemiological research has been to identify risk factors that predict the fraction of the exposed population that will contract arsenic-associated disease. Validated risk factors include the duration-weighted exposure level of arsenic, gender, nutritional status, genetic variations, and the efficiency of arsenic methylation during its metabolism. Understanding the effect and biological relevance of these risk factors has advanced the field, yet the epidemiological data suggest that there are still significant sources of disease risk that we have not yet identified. This proposal is based on the hypothesis that a key source of disease risk is individual variability in susceptibility to arsenic cytotoxicity, a phenomenon that has been observed in, as one example, limited studies of blood cells from arsenic-exposed humans. In this project we propose to utilize lymphoblastoid cell lines (LBLs) from a total of 130 individuals to characterize the individual variability in susceptibility to arsenic cytotoxicity. Genome-wide gene expression levels will be measured by RNA microarray analysis in order to identify genes whose expression levels correlate with arsenic-resistance level within this in vitro population. Candidate """"""""arsenic resistance"""""""" genes will be subject to experimental modulation of gene expression levels in order to validate their functional significance in conferring arsenic resistance. Finally, a set of functionally validated candidate genes that identify the level of arsenic susceptibility will be tested in primary blood cells sampled from individuals at high arsenic exposure compared to a corresponding group of individuals at low arsenic exposure. The long-term goal of this project is twofold: to provide mechanistic information about genes that can reduce arsenic cytotoxicity and to develop additional biomarkers of arsenic-associated disease risk, allowed more refined assessment of risk to real-world populations.

Public Health Relevance

Worldwide, many people suffer from disease caused or aggravated by exposure to arsenic in the environment. This project aims to understand why some people are particularly sensitive to the damaging effects of a level of arsenic that might not cause damage to other people. With this information we can advance our basic knowledge about how arsenic causes damage, as well as being better able to predict who, within a population of arsenic-exposed people will be at greatest risk of disease from that exposure.

National Institute of Health (NIH)
National Institute of Environmental Health Sciences (NIEHS)
Hazardous Substances Basic Research Grants Program (NIEHS) (P42)
Project #
Application #
Study Section
Special Emphasis Panel (ZES1-LWJ-M)
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of Arizona
United States
Zip Code
Youn, Jong-Sang; Csavina, Janae; Rine, Kyle P et al. (2016) Hygroscopic Properties and Respiratory System Deposition Behavior of Particulate Matter Emitted By Mining and Smelting Operations. Environ Sci Technol 50:11706-11713
Olivares, Christopher I; Sierra-Alvarez, Reyes; Abrell, Leif et al. (2016) Zebrafish embryo toxicity of anaerobic biotransformation products from the insensitive munitions compound 2,4-dinitroanisole. Environ Toxicol Chem 35:2774-2781
Rehman, Zahir Ur; Khan, Sardar; Qin, Kun et al. (2016) Quantification of inorganic arsenic exposure and cancer risk via consumption of vegetables in southern selected districts of Pakistan. Sci Total Environ 550:321-9
Zhong, Hua; Liu, Guansheng; Jiang, Yongbing et al. (2016) Effect of low-concentration rhamnolipid on transport of Pseudomonas aeruginosa ATCC 9027 in an ideal porous medium with hydrophilic or hydrophobic surfaces. Colloids Surf B Biointerfaces 139:244-8
Rodriguez-Freire, Lucia; Moore, Sarah E; Sierra-Alvarez, Reyes et al. (2016) Arsenic remediation by formation of arsenic sulfide minerals in a continuous anaerobic bioreactor. Biotechnol Bioeng 113:522-30
Beamer, Paloma I; Klimecki, Walter T; Loh, Miranda et al. (2016) Association of Children's Urinary CC16 Levels with Arsenic Concentrations in Multiple Environmental Media. Int J Environ Res Public Health 13:
Honeker, Linnea K; Root, Robert A; Chorover, Jon et al. (2016) Resolving colocalization of bacteria and metal(loid)s on plant root surfaces by combining fluorescence in situ hybridization (FISH) with multiple-energy micro-focused X-ray fluorescence (ME μXRF). J Microbiol Methods 131:23-33
Ezeh, Peace C; Xu, Huan; Lauer, Fredine T et al. (2016) Monomethylarsonous acid (MMA+3) Inhibits IL-7 Signaling in Mouse Pre-B Cells. Toxicol Sci 149:289-99
Gil-Loaiza, Juliana; White, Scott A; Root, Robert A et al. (2016) Phytostabilization of mine tailings using compost-assisted direct planting: Translating greenhouse results to the field. Sci Total Environ 565:451-61
Olivares, Christopher I; Wang, Junqin; Luna, Carlos D Silva et al. (2016) Continuous treatment of the insensitive munitions compound N-methyl-p-nitro aniline (MNA) in an upflow anaerobic sludge blanket (UASB) bioreactor. Chemosphere 144:1116-22

Showing the most recent 10 out of 425 publications