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LACK OF DNA SINGLE STRAND BREAKS IN A LUNG EPITHELIAL CELL LINE AFTER EXPOSURE TO ARSENIC
Molinelli, A., J. Nakamura, J. Swenberg, AND M. C. Madden. LACK OF DNA SINGLE STRAND BREAKS IN A LUNG EPITHELIAL CELL LINE AFTER EXPOSURE TO ARSENIC. Presented at Society of Toxicology, Baltimore, MD, March 21-25, 2004.
Arsenic (As) is a carcinogen whose most important target organs include the skin and lungs. Exposure can occur via water ingestion, or inhalation, as As is a by-product of fossil fuel combustion and other industrial activities. The carcinogenic mechanism of action for As remains unclear. One hypotheses proposes As induces cancer by creating oxidative stress. In previous studies we found modest evidence of increased peroxidation after exposure of BEAS-2B cells to inorganic As as arsenite (iAs). To study the possible mechanistic link between As exposure and lung carcinogenesis, we examined iAs induction of DNA single strand breaks (SSB) using a human bronchial epithelial cell line (BEAS-2B). SSBs were assessed via the comet assay, and a novel colorimetric assay that indirectly measures SSBs repair. This assay is based on the premise that DNA SSB's induce the activation of the repair enzyme poly(ADP-ribose)polymerase, which in turn depletes intracellular NAD+/NAD(P)H (Nucleic Acids Res. 31(17):e104, 2003). We did not find any statistically significant differences in DNA SSBs between the control and iAs (1nM-10uM) treated cells with the comet and NAD(P)H assays with up to 4h exposures at 37oC. Also, no increase in SSBs was observed when the cells were exposed at 4oC which inhibits DNA repair. In these studies, hydrogen peroxide and methyl methanesulfonate induced increased SSBs. These data suggest that iAs does not directly induce an increased SSBs in this cell line, possibly because BEAS-2B cells may be more resistant to damage than other extrapulmonary cell types shown to have increased SSBs upon iAs exposure. Furthermore, iAs can be converted in vivo to methylated organic species that may be more potent inducers of oxidative stress and SSBs. Further analyses into the possible contributions of the aforementioned factors is underway. [This abstract may not necessarily reflect official EPA policy. Supported by EPA/UNC CT827206].
Record Details:Record Type: DOCUMENT (PRESENTATION/ABSTRACT)
Organization:U.S. ENVIRONMENTAL PROTECTION AGENCY
OFFICE OF RESEARCH AND DEVELOPMENT
NATIONAL HEALTH AND ENVIRONMENTAL EFFECTS RESEARCH LABORATORY
HUMAN STUDIES DIVISION
CLINICAL RESEARCH BRANCH