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 (H D) and L-nitroarginine methyl ester (L-NAME) and then incubated at either 2 5 or 37 degrees C. Lowering the temperature of the cultures decreased the 2 4-h toxicity of HD, but did not increase the efficacy of L-NAME protection. However, the length of time post-ND treatment in which L-NAME was maximall y effective in protecting against HD toxicity was dramatically enhanced, ou t to 12 h after HD exposure. In addition, the persistence of L-NAME protect ion of the cells against HD was significantly lengthened. Tests conducted i n human skin keratinocytes also showed that lowering the incubation tempera ture of actively proliferating, just-confluent or post-confluent cultures s ignificantly and persistently decreased the cytotoxicity of HD. The persist ence 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 decr eased the severity of the resultant lesions out to 72 h post-exposure. Crow n Copyright (C) 1999 Elsevier Science Ireland Ltd.