Epidemiological studies have confirmed that inorganic arsenic is a human carcinogen. It is clear that the complex biotransformation pathways of arsenic undergoes produces several chemical forms of arsenic that vary greatly in their toxicological potency. Thus, it is reasonable to expect that human biotransformation of arsenic is key to its toxic effects. Arsenic biotransformation appears to have a considerable degree of inter-individual variability that has the characteristics of being heritably determined, suggested by a number of studies, including reports of familial aggregation of urinary arsenic metabolite levels. Thus, understanding the metabolism of arsenic is a prerequisite to understanding its toxicological effects in humans. This project will fully characterize the genetic variability of all known genes involved in arsenic biotransformation in a diverse group of ethnically defined, globally collected human samples of arsenic-exposed individuals. Within these populations we will conduct what we believe to be the largest genetic association study to date, with the aim of relating individual variation in arsenic metabolism, measured in two complementary ways-enzymatic activity and urinary metabolite levels, to variations in the DNA sequence of candidate genes involved in arsenic metabolism, including GSTO1-1, PNP, and CYT19. Subsequent Aims will be directed at expressing variant isoforms of candidate gene products and characterizing their biochemical activity to complement the genetic associations with mechanistic information. Finally, this project will continue the group's past success in efforts to identify new arsenic biotransformation pathway members. The successful completion of this work will provide one of the most comprehensive data sets describing the human biotransformation of arsenic, and will be a valuable resource to the scientific community, as well as the general community of stakeholders in the SBRP program.

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
Hazardous Substances Basic Research Grants Program (NIEHS) (P42)
Project #
2P42ES004940-16
Application #
6901470
Study Section
Special Emphasis Panel (ZES1-SET-A (S6))
Project Start
2005-04-01
Project End
2010-03-31
Budget Start
2005-04-01
Budget End
2006-03-31
Support Year
16
Fiscal Year
2005
Total Cost
$388,875
Indirect Cost
Name
University of Arizona
Department
Type
DUNS #
806345617
City
Tucson
State
AZ
Country
United States
Zip Code
85721
Valentín-Vargas, Alexis; Neilson, Julia W; Root, Robert A et al. (2018) Treatment impacts on temporal microbial community dynamics during phytostabilization of acid-generating mine tailings in semiarid regions. Sci Total Environ 618:357-368
Brusseau, Mark L (2018) Assessing the potential contributions of additional retention processes to PFAS retardation in the subsurface. Sci Total Environ 613-614:176-185
Delikhoon, Mahdieh; Fazlzadeh, Mehdi; Sorooshian, Armin et al. (2018) Characteristics and health effects of formaldehyde and acetaldehyde in an urban area in Iran. Environ Pollut 242:938-951
Hammond, Corin M; Root, Robert A; Maier, Raina M et al. (2018) Mechanisms of Arsenic Sequestration by Prosopis juliflora during the Phytostabilization of Metalliferous Mine Tailings. Environ Sci Technol 52:1156-1164
Yan, Ni; Zhong, Hua; Brusseau, Mark L (2018) The natural activation ability of subsurface media to promote in-situ chemical oxidation of 1,4-dioxane. Water Res 149:386-393
Madeira, Camila L; Field, Jim A; Simonich, Michael T et al. (2018) Ecotoxicity of the insensitive munitions compound 3-nitro-1,2,4-triazol-5-one (NTO) and its reduced metabolite 3-amino-1,2,4-triazol-5-one (ATO). J Hazard Mater 343:340-346
Liu, Pengfei; Rojo de la Vega, Montserrat; Sammani, Saad et al. (2018) RPA1 binding to NRF2 switches ARE-dependent transcriptional activation to ARE-NRE-dependent repression. Proc Natl Acad Sci U S A 115:E10352-E10361
Thomas, Andrew N; Root, Robert A; Lantz, R Clark et al. (2018) Oxidative weathering decreases bioaccessibility of toxic metal(loid)s in PM10 emissions from sulfide mine tailings. Geohealth 2:118-138
Yan, Ni; Liu, Fei; Liu, Boyang et al. (2018) Treatment of 1,4-dioxane and trichloroethene co-contamination by an activated binary persulfate-peroxide oxidation process. Environ Sci Pollut Res Int :
Dehghani, Mansooreh; Sorooshian, Armin; Nazmara, Shahrokh et al. (2018) Concentration and type of bioaerosols before and after conventional disinfection and sterilization procedures inside hospital operating rooms. Ecotoxicol Environ Saf 164:277-282

Showing the most recent 10 out of 497 publications