Toxicity of sulphur mustard in adult rat lung organ culture.

The toxicity of the chemical warfare agent sulphur mustard, (bis-(2-chloroethyl)sulphide, HD), was examined in adult rat lung organ cultures. Assessment of HD-induced damage by the MTT cytotoxicity assay indicated that the median lethal concentration (LC50) of HD in these cultures was reproducible, and in the microM range. Damage to the lung slices was expressed only after a latent period of 48 h and did not increase significantly with longer expression times. Histopathological examination of HD-treated lung cultures showed that the structural changes in the lung tissue paralleled the toxicity measured biochemically, and were also similar to the damage found in animals and man exposed to HD in vivo. This in vitro model offers a useful tool with which to study the toxicity and mechanism of action of sulphur mustard.

Cysteine esters protect cultured rodent lung slices from sulphur mustard.

1. In previous studies an in vitro rat lung slice system was used to investigate the metabolic and structural changes after exposure to known lung toxicants. 2. In this study, the same system was used to identify the ability of cysteine esters to protect against sulphur mustard toxicity. 3. The cyclopentyl (CCPE), cyclohexyl (CCHE), isopropyl (CIPE), methyl (CME) esters of cysteine, cystine dimethyl ester (CDME), cysteine (CySH) and N-acetyl cysteine (NAc) were all non-toxic to cultured rat lung slices at 5 mM (equivalent cysteine concentration) after a pretreatment time of 30 min. 4. Pretreatment with the isopropyl, cyclohexyl, cyclopentyl and methyl esters of cysteine at concentrations higher than 1 mM protected against an IC50 of sulphur mustard, however, neither cysteine nor N-acetylcysteine protected. 5. We propose that the extent of protection is directly related to increased levels of intracellular cysteine provided by the esters of cysteine.