Effect of lowered temperature on the toxicity of sulphur mustard in vitro and in vivo.
Primary cultures of chick embryo neurons were exposed to sulphur mustard (HD) and L-nitroarginine methyl ester (L-NAME) and then incubated at either 25 or 37 degrees C. Lowering the temperature of the cultures decreased the 24-h toxicity of HD, but did not increase the efficacy of L-NAME protection. However, the length of time post-HD treatment in which L-NAME was maximally effective in protecting against HD toxicity was dramatically enhanced, out to 12 h after HD exposure. In addition, the persistence of L-NAME protection of the cells against HD was significantly lengthened. Tests conducted in human skin keratinocytes also showed that lowering the incubation temperature of actively proliferating, just-confluent or post-confluent cultures significantly and persistently decreased the cytotoxicity of HD. The persistence of L-NAME protection was increased in non-proliferating cells. Finally, cooling of HD-vapour exposed sites on hairless guinea pigs for 4.5 h decreased the severity of the resultant lesions out to 72 h post-exposure.
Therapy Group, Medical Countermeasures Section, Defence Research Establishment Suffield, Alberta, Canada. thomas.sawyer@dres.dnd.ca
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D000818:Animals; D002478:Cells, Cultured; D002619:Chemical Warfare Agents / Q000633:toxicity*; D002642:Chick Embryo; D003080:Cold Temperature; D006168:Guinea Pigs; D006801:Humans; D015603:Keratinocytes / Q000187:drug effects; D009151:Mustard Gas / Q000633:toxicity*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects; D012867:Skin / Q000187:drug effects
D002619:Chemical Warfare Agents; D009151:Mustard Gas; D019331:NG-Nitroarginine Methyl Ester