Arsenic is cytotoxic and genotoxic to primary human lung cells.

Abstract

Arsenic originates from both geochemical and numerous anthropogenic activities. Exposure of the general public to significant levels of arsenic is widespread. Arsenic is a well-documented human carcinogen. Long-term exposure to high levels of arsenic in drinking water has been linked to bladder, lung, kidney, liver, prostate, and skin cancers. Among them, lung cancer is of great public concern. However, little is known about how arsenic causes lung cancer and few studies have considered effects in normal human lung cells. The purpose of this study was to determine the cytotoxicity and genotoxicity of arsenic in human primary bronchial fibroblast and epithelial cells. Our data show that arsenic induces a concentration-dependent decrease in cell survival after short (24h) or long (120h) exposures. Arsenic induces concentration-dependent but not time-dependent increases in chromosome damage in fibroblasts. No chromosome damage is induced after either 24h or 120h arsenic exposure in epithelial cells. Using neutral comet assay and gamma-H2A.X foci forming assay, we found that 24h or 120h exposure to arsenic induces increases in DNA double strand breaks in both cell lines. These data indicate that arsenic is cytotoxic and genotoxic to human lung primary cells but lung fibroblasts are more sensitive to arsenic than epithelial cells. Further research is needed to understand the specific mechanisms involved in arsenic-induced genotoxicity in human lung cells.

• Authors: Hong Xie, Shouping Huang, Sarah Martin, John P Wise Sr
• Journal: Mutation research. Genetic toxicology and environmental mutagenesis (Mutat Res Genet Toxicol Environ Mutagen) Vol. 760 Pg. 33-41 (Jan 15 2014) ISSN: 1383-5718 [Print] Netherlands
• PMID: 24291234 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2013 Elsevier B.V. All rights reserved.

Chemical References

• H2AX protein, human
• Histones
• Arsenic

Topics

• Arsenic (pharmacology)
• Bronchi (cytology)
• Cell Survival (drug effects)
• Cells, Cultured
• Chromosome Aberrations (drug effects)
• Comet Assay
• DNA Breaks, Double-Stranded (drug effects)
• DNA Damage
• Dose-Response Relationship, Drug
• Epithelial Cells (drug effects, metabolism)
• Fibroblasts (cytology, drug effects, metabolism)
• Fluorescent Antibody Technique
• Histones (metabolism)
• Humans
• Time Factors