Integrated study of arsenic-induced pulmonary toxicity

  • "Recent epidemiological evidence has clearly established the lung as a target organ for arsenic, sustaining both carcinogenic and degenerative diseases." - Clark Lantz

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Relevance to SWEHSC: 

Recent epidemiological evidence has clearly established the lung as a target organ for arsenic, sustaining both carcinogenic and degenerative diseases. This may be particularly relevant for the southwest, where the University of Arizona Superfund program has documented substantial airborne arsenic from mine tailings.

Cluster of Efforts: 
Investigators/Funding: Lantz (RFG2), Boitano (RFG2), Burgess (RFG2) USEPA/R832095, NIEHS/ES004940 (Superfund Component Project)
              Scott Boitano                 Jeff Burgess
  • In order to identify potential mechanisms of action and to identify biomarkers and adverse health effects, members of RFG2 have developed an integrated research approach, which includes in vitro assessment of the effects of As exposure on human airway epithelial cells (Dr. Scott Boitano) analysis of in vivo effects of arsenic in model animal systems (Dr. Clark Lantz) and validation of As-induced effects in human populations (Dr. Jeff Burgess).
  • Using an in vitro human bronchial epithelial model, the group has shown that arsenic can affect wound healing and produces increased levels of MMP-9. This appears to be due in part to a suppression of purinergic receptor activity and alterations in intracellular calcium.
  • Using an in vivo model of lung epithelial injury, Dr. Lantz has verified that similar changes in wound repair and alterations in junctional proteins occur in adult mice given 50 ppb arsenic in their drinking water for 4 weeks.
  • In human populations, Dr. Burgess has demonstrated remodeling-associated biomarker alterations in the sputum and serum of arsenic exposed individuals.
  • In his Superfund project, Dr. Lantz is investigating arsenic effects in lung development. He has previously shown that arsenic administered during in utero and early postnatal periods can lead to irreversible airway hyper-reactivity.
  • The study is currently focusing on the effect of folate supplementation on these responses. Increases in folate result in a suppression of the As-induced effects on smooth muscle. However, folate was only able to reduce the increased airway hyper-reactivity at low exposure levels.
  • In collaboration with Dr. Bernie Futscher (RFG1), Dr. Lantz has a grant application under review to determine the role of DNA methylation during lung development (R21HD066492, Elucidation of Epigenetically Controlled Gene Networks Important in Lung Development).
  • Drs. Burgess (RFG2) and O'Rourke (RFG2) are funded (EPA R833992, Modeling Dietary Contributions to Arsenic Dose and Methylation: Elucidating Predictive Linkages) to develop more accurate models of the sources of environmental arsenic, based on their preliminary funded studies demonstrating that drinking water arsenic levels are only roughly correlated with biomarkers of arsenic exposure in people.
  • Several Center investigators (Vercelli/RFG2, Boitano/RFG2, Chen/RFG2, Lantz/RFG2) have collaborated on a proposal for a NIEHS Children's Environmental Health and Disease Prevention Research Centers: Formative Centers (P20) grant application (Arizona Childrens' Center for Research on Environmental Health and Disease). The application has received an outstanding score and is awaiting a funding decision.