Sulphur mustard induced DNA damage in mice after dermal and inhalation exposure

Sulphur mustard (SM) is a chemical warfare agent of the blistering agent ca tegory for which there is still no effective therapy. SM, being a strong el ectrophile, readily reacts with a wide range of cellular macromolecules inc luding DNA, RNA and protein. Since the main intoxication routes for SM are inhalation and dermal penetration, in the present study we have exposed fem ale mice to different concentrations of SM by dermal and inhalation exposur es and estimated the DNA damage in different organs viz., liver, lung, sple en and thymus. SM was applied at 38.7, 77.4, 154.7 mg/kg body weight, on th e hair-clipped skin (dermal exposure) equivalent to 0.25, 0.5 and 1.0 of th e LD50. Inhalation exposure was carried out at 10.6, 21.2 and 42.3 mg/m(3) for 1 h duration equivalent to 0.25, 0.5 and 1.0 LC50. SM induced a dose-de pendent DNA damage in all the organs except the lung in dermal exposure. Si milarly the inhalation exposure resulted in dose- and time-dependent effect in all the organs including lung. By both routes of exposure liver was the most affected organ followed by spleen, thymus and lung in decreasing orde r. The quantitative data were corroborated by qualitative analysis of DNA o n agarose gel electrophoresis. The genomic DNA analysis of the organs had r evealed random nuclear DNA fragmentation resulting in a 'smear' typical of necrotic form of cell death. Since DNA damage is not reversible especially in liver, this can be used as a marker for SM exposure through either the d ermal or inhalation route. (C) 1999 Elsevier Science Ireland Ltd. All right s reserved.