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Inter strand crosslinks in DNA induced in vivo by percutaneous application of sulphur mustard to rats and mice
M. Richterova, R. Stetina, P. Jost, H. Svobodova, V. Rehacek, J. Kassa,
Language English Country Netherlands
Document type Journal Article
- MeSH
- DNA Adducts MeSH
- Chemical Warfare Agents toxicity MeSH
- Liver drug effects metabolism pathology MeSH
- Colon drug effects metabolism pathology MeSH
- Comet Assay MeSH
- Rats MeSH
- Humans MeSH
- Lymphocytes drug effects metabolism pathology MeSH
- Mice, Inbred BALB C MeSH
- Mice MeSH
- DNA Repair * MeSH
- DNA Damage * MeSH
- Rats, Wistar MeSH
- Cross-Linking Reagents administration & dosage toxicity MeSH
- Spleen drug effects metabolism pathology MeSH
- Mustard Gas administration & dosage toxicity MeSH
- Animals MeSH
- Check Tag
- Rats MeSH
- Humans MeSH
- Male MeSH
- Mice MeSH
- Female MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
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.
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- $a 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.
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