Inter-strand crosslinks (ICL) in the DNA are regarded to be the main toxic lesions induced by sulphur mustard (SM). We have followed the induction of ICL in the DNA of different organs of Wistar rats and Balb/c or NMRI mice by the percutaneous application of SM using the modified (reverse) comet assay. Significant amounts of ICL were found in Balb/C lymphocytes, in bone marrow and liver cells after the dose of 80 mg/kg. A dose-dependent amount of ICL was induced in rats, with efficient induction in lymphocytes and spleen cells already after 5 mg SM/kg, indicating a higher susceptibility of rats to the DNA-damaging effect of SM compared with mice. A significant induction of ICL in other tested tissues (liver, bone marrow, colon epithelium) was seen at the dose of 20 mg/kg. The induced ICL were removed from the DNA during 48 h except for rats at the dose of 80 mg/kg. In fact, we observed that ICL are almost completely repaired in tissues of rats receiving high lethal doses. Results suggest that the unhooking of ICL, which we followed with the comet assay, may lead to the formation of another toxic DNA lesion during the repair process.

Department of Toxicology and Military Pharmacy Faculty of Military Health Sciences University of Defence Trebesska 1575 500 01 Hradec Kralove Czech Republic

Department of Toxicology and Military Pharmacy Faculty of Military Health Sciences University of Defence Trebesska 1575 500 01 Hradec Kralove Czech Republic; Biomedical Research Centre University Hospital Hradec Kralove Sokolska 581 500 05 Hradec Kralove Czech Republic

Transfusion Department University Hospital Hradec Kralove Hradec Kralove Czech Republic

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