Project 3: Arsenic Biomarker Epidemiology. Arsenic is ranked number one on the Superfund Priority List of Hazardous Substances. During the last five years, we have found that early life exposure to arsenic results in major mortality increases among young adults aged 30-49 from lung cancer and bronchiectasis, myocardial infarction, kidney cancer, and bladder cancer. Our Chile studies have recently identified even more causes of death related to arsenic, and show that peak mortality risks are much greater than those from any other environmental exposure anywhere in the worid. We plan to continue our investigation of arsenic exposure and mortality in northern Chile for the years 1950 to 2000, now assessing mortality due to pulmonary tuberculosis, chronic renal failure, and our newly discovered evidence of increased mortality from cancers of the larynx, penis, cervix and thyroid gland. We will also follow a unique cohort of children in Bangladesh who were highly exposed to arsenic in utero and in early childhood, including measuring lung function, assessing the incidence of chronic respiratory disease and upper respiratory tract infections, measuring blood pressure, blood glucose and ;ff2-microglobulin, a marker of reduced kidney glomerular filtration rate. We will collect urine samples and buccal cells from Bangladesh and from our ongoing northern Chile eariy life exposure study, to analyze epigenetic alterations and proteomic biomarkers of arsenic exposure, susceptibility, and disease. We will use the northern Chile buccal and urine samples to assess the impact on pulmonary function and respiratory symptoms in adults, decades after high exposure. We will conduct in vitro studies to determine the mechanism and downstream effects involved in the persistent down-regulation of HBDl gene expression by the toxic arsenic metabolite, MMA3. We will also knock down HBDl gene expression in target organ cell lines to detennine the genes that are affected by HBDl down-regulation, in summary, we are proposing an integrated research strategy assessing multiple outcomes from arsenic exposure in population studies, focusing on effects from eariy life exposure, along with pursuing evidence concerning mechanisms of action.

Public Health Relevance

Arsenic is present in many Superi'und sites. We have shown marked increases in mortality among adults following eariy life exposure for several causes of death, with mortality increases much greater than from any other known environmental exposure. In our proposed new work, we will investigate new findings following childhood exposure, and will study the mechanisms of action by which arsenic produces them.

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
Hazardous Substances Basic Research Grants Program (NIEHS) (P42)
Project #
5P42ES004705-28
Application #
8838123
Study Section
Special Emphasis Panel (ZES1-SET-V)
Project Start
Project End
2017-03-31
Budget Start
2015-04-01
Budget End
2016-03-31
Support Year
28
Fiscal Year
2015
Total Cost
$281,568
Indirect Cost
$76,163
Name
University of California Berkeley
Department
Type
DUNS #
124726725
City
Berkeley
State
CA
Country
United States
Zip Code
94704
Rappaport, Stephen M (2018) Redefining environmental exposure for disease etiology. NPJ Syst Biol Appl 4:30
Tachachartvanich, Phum; Sangsuwan, Rapeepat; Ruiz, Heather S et al. (2018) Assessment of the Endocrine-Disrupting Effects of Trichloroethylene and Its Metabolites Using in Vitro and in Silico Approaches. Environ Sci Technol 52:1542-1550
Guyton, Kathryn Z; Rieswijk, Linda; Wang, Amy et al. (2018) Key Characteristics Approach to Carcinogenic Hazard Identification. Chem Res Toxicol :
Roh, Taehyun; Steinmaus, Craig; Marshall, Guillermo et al. (2018) Age at Exposure to Arsenic in Water and Mortality 30-40 Years After Exposure Cessation. Am J Epidemiol 187:2297-2305
Daniels, Sarah I; Chambers, John C; Sanchez, Sylvia S et al. (2018) Elevated Levels of Organochlorine Pesticides in South Asian Immigrants Are Associated With an Increased Risk of Diabetes. J Endocr Soc 2:832-841
Guyton, Kathryn Z; Rusyn, Ivan; Chiu, Weihsueh A et al. (2018) Application of the key characteristics of carcinogens in cancer hazard identification. Carcinogenesis 39:614-622
Grigoryan, Hasmik; Edmands, William M B; Lan, Qing et al. (2018) Adductomic signatures of benzene exposure provide insights into cancer induction. Carcinogenesis 39:661-668
Barazesh, James M; Prasse, Carsten; Wenk, Jannis et al. (2018) Trace Element Removal in Distributed Drinking Water Treatment Systems by Cathodic H2O2 Production and UV Photolysis. Environ Sci Technol 52:195-204
Counihan, Jessica L; Wiggenhorn, Amanda L; Anderson, Kimberly E et al. (2018) Chemoproteomics-Enabled Covalent Ligand Screening Reveals ALDH3A1 as a Lung Cancer Therapy Target. ACS Chem Biol 13:1970-1977
Lavy, Adi; Keren, Ray; Yu, Ke et al. (2018) A novel Chromatiales bacterium is a potential sulfide oxidizer in multiple orders of marine sponges. Environ Microbiol 20:800-814

Showing the most recent 10 out of 629 publications