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
Mora, Marco; Braun, Rachel A; Shingler, Taylor et al. (2017) Analysis of remotely sensed and surface data of aerosols and meteorology for the Mexico Megalopolis Area between 2003 and 2015. J Geophys Res Atmos 122:8705-8723
Guo, Zhilin; Brusseau, Mark L (2017) The impact of well-field configuration and permeability heterogeneity on contaminant mass removal and plume persistence. J Hazard Mater 333:109-115
Zhang, Xiang; Gu, Xiaogang; Lu, Shuguang et al. (2017) Application of ascorbic acid to enhance trichloroethene degradation by Fe(III)-activated calcium peroxide. Chem Eng J 325:188-198
Danish, Muhammad; Gu, Xiaogang; Lu, Shuguang et al. (2017) An efficient catalytic degradation of trichloroethene in a percarbonate system catalyzed by ultra-fine heterogeneous zeolite supported zero valent iron-nickel bimetallic composite. Appl Catal A Gen 531:177-186
Ramos-Ruiz, Adriana; Sesma-Martin, Juan; Sierra-Alvarez, Reyes et al. (2017) Continuous reduction of tellurite to recoverable tellurium nanoparticles using an upflow anaerobic sludge bed (UASB) reactor. Water Res 108:189-196
Madeira, Camila L; Speet, Samuel A; Nieto, Cristina A et al. (2017) Sequential anaerobic-aerobic biodegradation of emerging insensitive munitions compound 3-nitro-1,2,4-triazol-5-one (NTO). Chemosphere 167:478-484
Honeker, Linnea K; Neilson, Julia W; Root, Robert A et al. (2017) Bacterial Rhizoplane Colonization Patterns of Buchloe dactyloides Growing in Metalliferous Mine Tailings Reflect Plant Status and Biogeochemical Conditions. Microb Ecol 74:853-867
Fu, Xiaori; Gu, Xiaogang; Lu, Shuguang et al. (2017) Benzene oxidation by Fe(III)-catalyzed sodium percarbonate: matrix constituent effects and degradation pathways. Chem Eng J 309:22-29
Olivares, Christopher I; Madeira, Camila L; Sierra-Alvarez, Reyes et al. (2017) Environmental Fate of 14C Radiolabeled 2,4-Dinitroanisole in Soil Microcosms. Environ Sci Technol 51:13327-13334
Soltani, Naghmeh; Keshavarzi, Behnam; Sorooshian, Armin et al. (2017) Oxidative potential (OP) and mineralogy of iron ore particulate matter at the Gol-E-Gohar Mining and Industrial Facility (Iran). Environ Geochem Health :

Showing the most recent 10 out of 460 publications