Grant Number:
Principal Investigator:
Burchiel, Scott W
Institution:
University of New Mexico Health Sciences Center
Most Recent Award Year:
2014
Exposures:
Air Pollutants:
Polycyclic aromatic hydrocarbons (PAHs)
Metals:
Arsenic
Health Outcomes:
Immune Outcomes:
Immunosuppression
Respiratory Outcomes:
Airway inflammation; Lung function
Biological Sample:
Blood; Human peripheral blood mononuclear cells; Urine
Environmental Sample:
Drinking water sample
Other Participant Data:
Respiratory infections from study clinic, self-reported, and the medical records; Lung function measured via including FVC, FEV1, and their ratio; Airway inflammation measured via exhaled nitric oxide
Abstract:
This ViCTER application supplements an RO1 from the PI that seeks to understand the mechanisms of immunosuppression produced by polycyclic aromatic hydrocarbons (PAHs) and arsenic alone and in combination following exposure of mice and humans. The underlying RO1 grant tests the hypothesis that arsenic produces synergistic immunosuppression with PAHs which are contained in tobacco smoke by inhibiting DNA repair of PAH bulky adducts. The PI's lab has demonstrated synergistic immunosuppression by PAHs and arsenic in vivo in mice and in vitro in human peripheral blood mononuclear cells (HPBMC). This ViCTER grant supports three highly interactive projects which significantly expand the original aims of the parent RO1 grant. All three projects rely upon the HEALS cohort in Bangladesh that has been studied by Columbia University and the University of Chicago with regard to drinking water arsenic exposures. The present study has been designed by our collaborator Dr. Factor-Litvak (Columbia Univ Superfund Program), the key epidemiologist for the HEALS study, to examine 200 study subjects in a 2x2 design of 50 per group of male smokers and nonsmokers who are also exposed to low or high arsenic in water. In Aim 1, Dr. Burchiel's lab will examine HPBMC obtained from these groups with known arsenic and PAH exposure data. Dr. Burchiel will work with the other two PI's, Dr. Parvez (Project 2, Columbia Univ) and Dr. Santella (Project 3, Columbia Univ), to test the hypothesis that in vivo exposure of humans to cigarette smoke and arsenic produces synergistic immunosuppression of T cell proliferation, T cell differentiation, and T cell/HPBMC cytokine production. Project 1 relies upon Project 2 to measure cytokine production as well as to provide relevant health endpoints, including lung function and upper airway infection assessments. Project 1 also relies upon Project 3 to measure biomarkers of exposure in the urine from study subjects (1-hydroxypyrene, 1-OHP) and PAH-DNA adducts in HPBMC. Dr. Parvez's Project 2 will assess several lung function endpoints of interest to the other investigators as well as examine mechanisms of oxidative stress and cytokine production that may correlate with inflammatory lung disease. Dr. Santella (Project 3) has had a longstanding interest in PAH-DNA adducts in HPBMC and benefits from this study by assisting in testing the hypothesis that high arsenic exposure potentiates PAH adduct formation, which might be a useful biomarker of co-exposures. Project 2 performs the recruitment for the study, and the overall coordination of sample collection, record keeping and data collection, and analysis which is overseen by an Administrative Core. In summary, this ViCTER program is highly integrated, benefits all investigators, and will add substantial new knowledge to immunologic and pulmonary health effects of combined cigarette smoke (surrogate for PAHs) and arsenic exposures, which present a huge public health burden.
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Related NIEHS-Funded Study Populations
Health Effects of Arsenic Longitudinal Study (HEALS)
Principal Investigator:
Ahsan, Habibul; Graziano, Joseph
| Study Population Page Study Population c63
Institution:
University of Chicago
Location:
Araihazar, Bangladesh
Number of Participants::
~35,000 recruited; Recruitment goal of 50,000
Brief Description::
This large prospective cohort study is based on individual-level data from a population exposed to a wide range of inorganic arsenic from drinking water in Araihazar, Bangladesh. Since 2000, the study has recruited more than 35,000 men and women with extensive questionnaire data, biological samples, drinking water samples, and diagnostic/clinical data.