Oprava poškození DNA vyvolaného sirným yperinem a jeho vztah k cytotoxicitě

• Main Author: Jílková, Martina
• Other Authors: Vopršalová, Marie
• Format: Dissertation
• Language: Czech
• Published: 2008
• Online Access: http://www.nusl.cz/ntk/nusl-292499

The aim of this study was to investigate the induction and repair mechanisms of DNA damage caused by sulphur mustard in specific cell lines and their relationship to cytotoxicity of sulphur mustard. Sulphur mustard is a chemical warfare agent of the blistering agent category, which can be misused in local conflicts, terrorist attacks and during liquidation of its storage. Sulphur mustard is an alkylating agent, which interacts with a wide range of cellular macromolecules including DNA, RNA and proteins. Sulphur mustard forms single - strand breaks, monofunctional guanine and adenine adducts, as well as interstrand cross-links involving the two guanines in interaction with DNA. This study is aimed at cross-links. We used the Single Cell Gel Electrophoresis (SCGE, comet assay) for their detection. It is a method of evaluation of single cells ambeded in agarose. It is used for detection of DNA single strand breaks in a single cell. In our modification of the method we determined cross-links, which make the alkaline DNA unwinding impossible. That is why we had to induce a standard number of single strand breaks in DNA by styreneoxide (at a certain concentration and exposure time) before the comet assay. We studied DNA repair mechanisms of specific DNA lesions using specific cell lines with clearly...