Ionic dependence of sulphur mustard cytotoxicity

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Authors
  1. Sawyer, T.W.
  2. Nelson, P.
  3. Bjarnason, S.
  4. Vair, C.
  5. Shei, Y.
  6. Tenn, C.
  7. Lecavalier, P.
  8. Burczyk, A.
Corporate Authors
Defence R&D Canada - Suffield, Ralston ALTA (CAN)
Abstract
The effect of ionic environment on sulphur mustard (bis 2-chloroethyl sulphide; HD) toxicity was examined in CHO-K1 cells. Cultures were treated with HD in different ionic environments at constant osmolar conditions (320 mOsM, pH 7.4). The cultures were refed with fresh culture medium 1 h after HD exposure, and viability was assessed. Little toxicity was apparent when HD exposures were carried out in ion-free sucrose buffer compared to LC50 values of -100-150 µM when the cultures were treated with HD in culture medium. Addition of NaCl to the buffer increased HD toxicity in a salt concentration-dependent manner to values similar to those obtained in culture medium. HD toxicity was dependent on both cationic and anionic species with anionic environment playing a much larger role in determining toxicity. Substitution of Nal for NaCl in the treatment buffers increased HD toxicity by over 1000%. The activity of the sodium hydrogen exchanger (NHE) in recovering from cytosolic acidification in salt-free and in different chloride salts did not correlate with the HD-induced toxicity in these buffers. However, the inhibition by HD of intracellular pH regulation correlated with its toxicity in NaCl, Nal and sucrose buffers. Analytical chemical studies and the toxicity of the iodine mustard derivative ruled out the role of chemical reactions yielding differentially toxic species as being responsible for the differences in HD toxicity observed. This work demonstrates that the
Report Number
DRDC-SUFFIELD-SL-2010-036 — Scientific Literature
Date of publication
01 Jun 2010
Number of Pages
12
Reprinted from
Toxicology and Applied Phamacology, vol 247, 2010, p 179-190
DSTKIM No
CA034922
CANDIS No
534443
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