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Principal Investigator: Lantz, Robert Clark
Institute Receiving Award University Of Arizona
Location Tucson, AZ
Grant Number R01ES027013
Funding Organization National Institute of Environmental Health Sciences
Award Funding Period 01 May 2017 to 31 Mar 2022
DESCRIPTION (provided by applicant): Abstract Arsenic is a ubiquitous environmental toxicant, found in high concentrations in water worldwide; more than 150 million people live in areas with the arsenic content significantly higher than the WHO and USEPA recommended guidelines (10 ppb).The lung is a target organ for arsenic toxicity. Reports from human studies in Chile, Bangladesh, Inner Mongolia and the West Bengal region of India show that chronic exposure to arsenic via drinking water is correlated with increased incidence of chronic cough, chronic bronchitis, shortness of breath, decreased lung function, and obstructive or restrictive lung disease. Evidence from our laboratory and others have contributed to a growing concern that even at 10 ppb, arsenic can alter lung structure and function. In addition, there is also growing evidence that in utero and early postnatal exposures to arsenic can lead to alterations in lung structure and function that contribute to the development of chronic lung disease later in life. In rural areas of United States such as in the southwestern region, a significant percentage of the population receives their water from private, unregulated wells where concentrations of arsenic can far exceed the 10 ppb level. In addition, dusts in the arid Southwestern United States can contain high levels of arsenic and other contaminants. Inhalation of these dusts can increase lung exposures to arsenic that mimic arsenic ingestion induced lung disease. Little data exist concerning the risk from exposure to arsenic containing dusts and the potential interactions between arsenic ingestion in water and dust exposures. Despite the accepted fact that the lung is a major target organ for arsenic toxicity, studies on biomarkers or mechanisms of non-malignant lung diseases following early life arsenic exposures are limited. One exception is Club (formerly Clara) cell secretory protein (hereafter CC16) that is dramatically reduced in blood and lungs of current smokers and is associated with decreased subsequent incidence of airflow limitation, accelerated decline of lung function, and mortality. Studies strongly support CC16 as a biomarker for lung function deterioration and a direct role for CC16 in protecting against chronic lung disease. However, specific function for CC16 in arsenic-induced lung abnormality remains ill-defined. Our overall objective is to determine the mechanism by which arsenic alters CC16 production and the role of reduced CC16 in altering lung structure and function following early life exposure to arsenic. Two Aims will be addressed. Aim.1 will determine the role of CC16 in arsenic-induced lung structural and functional alterations following early life exposures and Aim2 will determine the effect of arsenic exposure on CC16 production and its mode of action in the lung. Results from our study will establish the validity of CC16 as a biomarker for early life arsenic exposure and for the assessment of arsenic toxicity on long-term lung health. The elucidated mechanism will also help to establish therapeutic interventions in the treatment of arsenic-induced lung disease.
Science Code(s)/Area of Science(s) Primary: 69 - Respiratory
Publications See publications associated with this Grant.
Program Officer Srikanth Nadadur
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