# Arsenic exposure, CC16 and its effect on pulmonary function

> **NIH NIH R01** · UNIVERSITY OF ARIZONA · 2020 · $345,375

## Abstract

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 e...

## Key facts

- **NIH application ID:** 9892007
- **Project number:** 5R01ES027013-04
- **Recipient organization:** UNIVERSITY OF ARIZONA
- **Principal Investigator:** Yin Chen
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $345,375
- **Award type:** 5
- **Project period:** 2017-05-01 → 2022-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9892007

## Citation

> US National Institutes of Health, RePORTER application 9892007, Arsenic exposure, CC16 and its effect on pulmonary function (5R01ES027013-04). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/9892007. Licensed CC0.

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