Journal
TOXICOLOGY AND INDUSTRIAL HEALTH
Volume 23, Issue 4, Pages 209-221Publisher
SAGE PUBLICATIONS INC
DOI: 10.1177/0748233707083541
Keywords
ebselen; in vitro toxicology; nitrogen mustard
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Nitrogen mustards are vesicants capable of burning the skin, eyes and respiratory tract of exposed individuals. While generally less toxic than sulfur mustards, these compounds have the potential for use as chemical warfare agents. Presently, no antidote exists for treatment against nitrogen mustard toxicity. The purpose of this study was to investigate the in vitro toxicity of the nitrogen mustard mechlorethamine (HN2) in four cell models: CEM-SS human T cells, A431 human skin epithelial cells, rat hippocampal astrocytes and rat pleural mesothelial cells. Furthermore, the efficacy of the synthetic seleno-organic compound ebselen (Eb) (2-phenyl-1,2- benzisoselenazol-3(2H)-one) as a cytoprotective agent against such toxicity was evaluated. Significant increases in cell viability, as assessed using an MTT assay for viability, was demonstrated when 30 mu M Eb was used as a cotreatment with HN2 in all cell models tested at the following doses of HN2: A431 skin cells, 10-40 mu M; rat astrocytes, 20 and 40 mu M; rat mesothelia, 10-40 mu M; and human T cells 4-16 mu M. Decreases in cell viability and toxicity to HN2 were confirmed using light and scanning electron microscopy. Membrane damage, observed with HN2 exposure, such as blebbing and loss of cell projections, was ameliorated with Eb cotreatment. Our results demonstrate a generalized protective effect observed with Eb cotreatment that suggests that this agent may have potential as an antidote for HN2 exposure and toxicity.
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