Clark Lantz

CRIMSON preliminary data

 

Investigators

Clark Lantz, Ph.D.
Professor
Cellular & Molecular Medicine

 

Yin Chen, Ph.D
Associate Professor

Pharmacology and Toxicology

Amount of funding received:

5,000

Description:

Article published in Journal of Exposure Science & Environmental Epidemiology

Relevance to Swehsc : 

Environmental Arsenic Exposure, Selenium and Sputum alpha-1 Antitrypsin

Cluster of Efforts: 

Significant decreases in alpha-1-antitrypsin were seen in induced sputum from adult populations exposed to low levels of arsenic in their drinking water (20 ppb).  Decreases in this enzyme have previously been associated with the development of chronic obstructive pulmonary disease and lung cancer. 

Effect of Environmental Exposures to Arsenic

Relevance to Swehsc : 

Arsenic is a major environmental toxicant, not only in the Southwestern United States, but also throughout the world. Understanding the effects of inhaled arsenic in arid climates is particularly relevant.

Cluster of Efforts: 

Investigators: 

  • Jefferey Burgess, MD, MPH
  • Scott Boitano, PhD
  • Yin Chen, PhD
  • Margaret Kurzius-Spencer, PhD
  • R. Clark Lantz, PhD
Milestones: 
  • Significant decreases in a-1-antitrypsin were seen in induced sputum from adult populations exposed to low levels of arsenic in their drinking water. (Burgess, Boitano, Kurzius-Spencer, Lantz)
  • Children (ages 6-12) who have been exposed to arsenic in their drinking water during in utero and early life show decrements in lung function. (Lantz)
  • In utero and early postnatal inhalation exposure to real world dusts collected at a legacy mine site lead to alterations in lung function (increased airway reactivity). (Boitano, Lantz)
  • Arsenic Exposure through drinking water alters lung expression of genes and proteins involved in epithelial to mesenchymal transition (EMT). (Boitano, Lantz)
  • Animals exposed to arsenic have decreased expression levels of club (Clara) cell secretroy protein (CCSP). (Chen)

RFG2 Research Theme: Effect of Environmental Exposures to Arsenic

Arsenic is a major environmental toxicant, not only in the Southwestern United States, but also throughout the world. Understanding the effects of inhaled arsenic in arid climates is particularly relevant.

Environmental arsenic exposure, selenium and sputum alpha-1 Antitrypsin

Relevance to Swehsc : 

Exposure to arsenic in drinking water is associated with increased respiratory disease. Alpha-1 antitrypsin (AAT) protects the lung against tissue destruction. The objective of this study was to determine whether arsenic exposure is associated with changes in airway AAT concentration and whether this relationship is modified by selenium. A total of 55 subjects were evaluated in Ajo and Tucson, Arizona.

Cluster of Efforts: 

         

Milestones: 

Tap water and first morning void urine were analyzed for arsenic species, induced sputum for AAT and toenails for selenium and arsenic. Household tap-water arsenic, toenail arsenic and urinary inorganic arsenic and metabolites were significantly higher in Ajo (20.6 +/- 3.5 μg/l, 0.54 +/- 0.77 μg/g and 27.7 +/- 21.2 μg/l, respectively) than in Tucson (3.9 +/-2.5 μg/l, 0.16+/-0.20 μg/g and 13.0 +/-13.8 μg/l, respectively). In multivariable models, urinary monomethylarsonic acid (MMA) was negatively, and toenail selenium positively associated with sputum AAT (P = 0.004 and P = 0.002, respectively). In analyses stratified by town, these relationships remained significant only in Ajo, with the higher arsenic exposure. Reduction in AAT may be a means by which arsenic induces respiratory disease, and selenium may protect against this adverse effect.

 

HIGHLIGHTS not yet published

 

  • Beamer - Assessment of exposure levels and sources of arsenic and other metal exposure downwind from a legacy superfund mine site.  Levels were correlated with the urinary arsenic levels in the exposed population.

 

  • Vercelli - The discovery of the central role played by microbial diversity in the asthma-protective and allergy-protective effects of farming warrants metagenomic studies that concertedly and longitudinally investigate the microbiome, the genome, and the immune system.

 

  • Lantz/Boitano – arsenic can affect epithelial to mesenchymal transition in the lung.  Alterations are reduced with high folate diets

 

Integrated study of arsenic-induced pulmonary toxicity

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
Milestones: 
  • 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.

 

UA Science Internship Pairs High School Students, Research Mentors

News Date: 
June 3, 2013 :00am

Each year many SWEHSC researchers host high school students in their laboratories. Facility managers assits them process their samples and understand their data. SWEHSC members teach them about toxicology and environmental health. The program was designed by the SWEHSC Outreach Core and is conducted in collaboration with the BIO5 Instutue. Read more about this year's program

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