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Inter strand crosslinks in DNA induced in vivo by percutaneous application of sulphur mustard to rats and mice

TitleInter strand crosslinks in DNA induced in vivo by percutaneous application of sulphur mustard to rats and mice
Publication TypeJournal Article
Year of Publication2018
AuthorsRichterova M., Stetina R., Jost P., Svobodova H., Rehacek V., Kassa J.
JournalMutat Res Genet Toxicol Environ Mutagen
Volume832-833
Pagination35-40
Date PublishedAug
ISBN Number1383-5718 (Linking)
Accession Number30057019
KeywordsComet Assay, DNA crosslinks in vivo, Percutaneous application, sulphur mustard
Abstract

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 80mg/kg. A dose-dependent amount of ICL was induced in rats, with efficient induction in lymphocytes and spleen cells already after 5mg 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 20mg/kg. The induced ICL were removed from the DNA during 48h except for rats at the dose of 80mg/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.

URLhttps://www.ncbi.nlm.nih.gov/pubmed/30057019
DOI10.1016/j.mrgentox.2018.06.014
Short TitleInter strand crosslinks in DNA induced in vivo by percutaneous application of sulphur mustard to rats and mice

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