Effect of lowered temperature on the toxicity of sulphur mustard in vitro and in vivo

• Published in: Toxicology (Amsterdam) 1999-05, Vol.134 (1), p.27-37
• Main Authors: Sawyer, Thomas W., Risk, Darrell
• Format: Article
• Language: English
• Subjects: Animals; Biological and medical sciences; Cells, Cultured; Chemical and industrial products toxicology. Toxic occupational diseases; Chemical warfare agent; Chemical Warfare Agents - toxicity; Chick Embryo; Cold Temperature; Gas, fumes; Guinea Pigs; Hairless guinea pig; Human skin keratinocyte culture; Humans; Hypothermia; Keratinocytes - drug effects; l-nitroarginine methyl ester, L-NAME; Medical sciences; Mustard Gas - toxicity; Neuron culture; Neurons - drug effects; NG-Nitroarginine Methyl Ester - pharmacology; Protection; Skin - drug effects; Sulphur mustard, bis(2-chloroethyl) sulphide, HD; Temperature; Toxicity; Toxicology
• ISSN: 0300-483X; 1879-3185
• DOI: 10.1016/S0300-483X(99)00019-0

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°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.