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| Description
| - Although platinum based cytostatic drugs have been successfully used in the chemotherapy of cancer for more than 30 years, its biochemical mechanism of action is still unclear. The current accepted opinion about their mechanism of action is that the drugs induce their cytotoxic properties through binding to the nuclear DNA and subsequent interference with normal transcription, and/or DNA replication mechanisms. Nevertheless a cell has several mechanisms to prevent them from binding to the nuclear DNA. The main aim of this work was to investigate affecting of binding of cisplatin to the nuclear DNA by the presence of glutathione (GSH), which can be considered as one of the possible molecules connected with occurring of drug resistance. Primarily we attempted to study the interactions between cisplatin and GSH using flow injection analysis with electrochemical detection (FIA-ED). The detecton limit for GSH was 100 pg mL-1. It clearly follows from the results obtained that the optimized technique is suitable to investigate the interaction between GSH and cisplatin. Moreover, we evaluated the formation of the complex by spectrometry. The spectrometric results obtained were in good agreement with electrochemical ones. After that we suggested the experimental scheme, where the mixture of GSH, DNA and cisplatin has been kept several hours under specific experimental conditions. The products of this interaction was analysed using various analytical techniques, electrochemical biosensor to detect Pt-DNA adducts, FIA-ED to analyse Pt-GSH complexes and liquid chromatography with mass spectrometry to evaluate the results obtained by the electrochemical techniques.
- Although platinum based cytostatic drugs have been successfully used in the chemotherapy of cancer for more than 30 years, its biochemical mechanism of action is still unclear. The current accepted opinion about their mechanism of action is that the drugs induce their cytotoxic properties through binding to the nuclear DNA and subsequent interference with normal transcription, and/or DNA replication mechanisms. Nevertheless a cell has several mechanisms to prevent them from binding to the nuclear DNA. The main aim of this work was to investigate affecting of binding of cisplatin to the nuclear DNA by the presence of glutathione (GSH), which can be considered as one of the possible molecules connected with occurring of drug resistance. Primarily we attempted to study the interactions between cisplatin and GSH using flow injection analysis with electrochemical detection (FIA-ED). The detecton limit for GSH was 100 pg mL-1. It clearly follows from the results obtained that the optimized technique is suitable to investigate the interaction between GSH and cisplatin. Moreover, we evaluated the formation of the complex by spectrometry. The spectrometric results obtained were in good agreement with electrochemical ones. After that we suggested the experimental scheme, where the mixture of GSH, DNA and cisplatin has been kept several hours under specific experimental conditions. The products of this interaction was analysed using various analytical techniques, electrochemical biosensor to detect Pt-DNA adducts, FIA-ED to analyse Pt-GSH complexes and liquid chromatography with mass spectrometry to evaluate the results obtained by the electrochemical techniques. (cs)
- I když platina založené cytostatika byly úspěšně použity v chemoterapii rakoviny pro více než 30 let, jeho biochemický mechanismus účinku je stále nejasná.Aktuální přijímaný názor o mechanismu jejich účinku je, že tyto léky vyvolat své cytotoxické vlastnosti prostřednictvím vazby na jadernou DNA a následné rušení s normálním přepisem a / nebo DNA replikace mechanismy. Přesto buňka má několik mechanismů, aby jim brání v navázání na jaderné DNA.Hlavním cílem této práce bylo zjistit vliv vazby cisplatiny na jaderné DNA v přítomnosti glutathionu (GSH), který lze považovat za jeden z možných molekul spojených s vyskytující lékové rezistence. V první řadě jsme se pokusili studovat interakcí mezi cisplatinou a GSH pomocí průtokové injekční analýzy s elektrochemickou detekcí (FIA-ED).Limit pro detecton GSH byla 100 pg ml-1. Z toho jasně vyplývá z výsledků získaných, že optimální postup je vhodné zkoumat interakci mezi GSH a cisplatinou. Kromě toho jsme hodnotili vznik komplexu spektrometrií. V spektrometrické Získané výsledky byly v dobré shodě s těmi electrochemical. Poté, co jsme navrhli experimentální schéma, kde se směs GSH, DNA a cisplatinou drženi několik hodin, za určitých experimentálních podmínek. Výrobky této interakce byl analyzován pomocí různých analytických technik, elektrochemický biosenzor pro detekci Pt-DNA adukty, FIA-ED analyzovat Pt-GSH komplexy a kapalinové chromatografie s hmotnostní spektrometrií vyhodnotit výsledky získané v elektrochemických technik. (en)
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| Title
| - Study of binding of platinum based cytostatics to DNA structure; Influence of glutathione
- Study of binding of platinum based cytostatics to DNA structure; Influence of glutathione (cs)
- Studium vazby platinových cytostatik na bázi DNA struktury; Vliv glutathionu (en)
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| skos:prefLabel
| - Study of binding of platinum based cytostatics to DNA structure; Influence of glutathione
- Study of binding of platinum based cytostatics to DNA structure; Influence of glutathione (cs)
- Studium vazby platinových cytostatik na bázi DNA struktury; Vliv glutathionu (en)
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| skos:notation
| - RIV/62156489:43210/07:00185066!RIV12-AV0-43210___
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| http://linked.open...avai/riv/aktivita
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| http://linked.open...avai/riv/aktivity
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| http://linked.open...iv/cisloPeriodika
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| http://linked.open...vai/riv/dodaniDat
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| http://linked.open...aciTvurceVysledku
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| http://linked.open.../riv/druhVysledku
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| http://linked.open...iv/duvernostUdaju
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| http://linked.open...titaPredkladatele
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| http://linked.open...dnocenehoVysledku
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| http://linked.open...ai/riv/idVysledku
| - RIV/62156489:43210/07:00185066
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| http://linked.open...riv/jazykVysledku
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| http://linked.open.../riv/klicovaSlova
| - cytostatics; glutathione; DNA (en)
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| http://linked.open.../riv/klicoveSlovo
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| http://linked.open...odStatuVydavatele
| - CH - Švýcarská konfederace
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| http://linked.open...ontrolniKodProRIV
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| http://linked.open...i/riv/nazevZdroje
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| http://linked.open...in/vavai/riv/obor
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| http://linked.open...ichTvurcuVysledku
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| http://linked.open...cetTvurcuVysledku
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| http://linked.open...vavai/riv/projekt
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| http://linked.open...UplatneniVysledku
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| http://linked.open...v/svazekPeriodika
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| http://linked.open...iv/tvurceVysledku
| - Adam, Vojtěch
- Beklová, Miroslava
- Eckschlager, Tomáš
- Hraběta, Jan
- Horna, Aleš
- Húska, Dalibor
- Kizek, René
- Křížková, Soňa
- Průša, Richard
- Trnková, Libuše
- Zítka, Ondřej
- Kukacka, J.
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| issn
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| number of pages
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| http://localhost/t...ganizacniJednotka
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