title: 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.affiliation: Wise Laboratory of Environmental and Genetic Toxicology, University of Southern Maine, Portland, ME, United States; Maine Center for Toxicology and Environmental Health, University of Southern Maine, Portland, ME, United States. Electronic address: hongxie@usm.maine.edu.
authors.forename: Hong
authors.initials: H
authors.lastname: Xie
authors.affiliation: Wise Laboratory of Environmental and Genetic Toxicology, University of Southern Maine, Portland, ME, United States; Maine Center for Toxicology and Environmental Health, University of Southern Maine, Portland, ME, United States.
authors.forename: Shouping
authors.initials: S
authors.lastname: Huang
authors.affiliation: Wise Laboratory of Environmental and Genetic Toxicology, University of Southern Maine, Portland, ME, United States.
authors.forename: Sarah
authors.initials: S
authors.lastname: Martin
authors.affiliation: Wise Laboratory of Environmental and Genetic Toxicology, University of Southern Maine, Portland, ME, United States; Maine Center for Toxicology and Environmental Health, University of Southern Maine, Portland, ME, United States.
authors.forename: John P
authors.initials: JP
authors.lastname: Wise
mesh_terms: D001151:Arsenic / Q000494:pharmacology*; D001980:Bronchi / Q000166:cytology; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002869:Chromosome Aberrations / Q000187:drug effects*; D020552:Comet Assay; D053903:DNA Breaks, Double-Stranded / Q000187:drug effects; D004249:DNA Damage; D004305:Dose-Response Relationship, Drug; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D006657:Histones / Q000378:metabolism; D006801:Humans; D013997:Time Factors
chemical_list: C468783:H2AX protein, human; D006657:Histones; D001151:Arsenic
keywords: Arsenic; Chromosome aberration; DNA double strand breaks; Genotoxicity; Human lung epithelial cells; Human lung fibroblasts