. "Study of binding of platinum based cytostatics to DNA structure; Influence of glutathione" . . "12"^^ . "K\u0159\u00ED\u017Ekov\u00E1, So\u0148a" . "Adam, Vojt\u011Bch" . . "Horna, Ale\u0161" . "1010-4283" . . . . "RIV/62156489:43210/07:00185066" . "CH - \u0160v\u00FDcarsk\u00E1 konfederace" . "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." . "Studium vazby platinov\u00FDch cytostatik na b\u00E1zi DNA struktury; Vliv glutathionu"@en . . . . "Study of binding of platinum based cytostatics to DNA structure; Influence of glutathione"@cs . . "P(IAA401990701)" . . "1"^^ . "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 . "Tumor Biology" . "cytostatics; glutathione; DNA"@en . "9" . . "Studium vazby platinov\u00FDch cytostatik na b\u00E1zi DNA struktury; Vliv glutathionu"@en . . . . "Trnkov\u00E1, Libu\u0161e" . "Pr\u016F\u0161a, Richard" . . "Z\u00EDtka, Ond\u0159ej" . "[D27E692B9931]" . "H\u00FAska, Dalibor" . . . . "RIV/62156489:43210/07:00185066!RIV12-AV0-43210___" . . "Kizek, Ren\u00E9" . "Kukacka, J." . . . "43210" . "453226" . . "Study of binding of platinum based cytostatics to DNA structure; Influence of glutathione"@cs . "28" . "Eckschlager, Tom\u00E1\u0161" . "Hrab\u011Bta, Jan" . "Study of binding of platinum based cytostatics to DNA structure; Influence of glutathione" . "9"^^ . "I kdy\u017E platina zalo\u017Een\u00E9 cytostatika byly \u00FAsp\u011B\u0161n\u011B pou\u017Eity v chemoterapii rakoviny pro v\u00EDce ne\u017E 30 let, jeho biochemick\u00FD mechanismus \u00FA\u010Dinku je st\u00E1le nejasn\u00E1.Aktu\u00E1ln\u00ED p\u0159ij\u00EDman\u00FD n\u00E1zor o mechanismu jejich \u00FA\u010Dinku je, \u017Ee tyto l\u00E9ky vyvolat sv\u00E9 cytotoxick\u00E9 vlastnosti prost\u0159ednictv\u00EDm vazby na jadernou DNA a n\u00E1sledn\u00E9 ru\u0161en\u00ED s norm\u00E1ln\u00EDm p\u0159episem a / nebo DNA replikace mechanismy. P\u0159esto bu\u0148ka m\u00E1 n\u011Bkolik mechanism\u016F, aby jim br\u00E1n\u00ED v nav\u00E1z\u00E1n\u00ED na jadern\u00E9 DNA.Hlavn\u00EDm c\u00EDlem t\u00E9to pr\u00E1ce bylo zjistit vliv vazby cisplatiny na jadern\u00E9 DNA v p\u0159\u00EDtomnosti glutathionu (GSH), kter\u00FD lze pova\u017Eovat za jeden z mo\u017En\u00FDch molekul spojen\u00FDch s vyskytuj\u00EDc\u00ED l\u00E9kov\u00E9 rezistence. V prvn\u00ED \u0159ad\u011B jsme se pokusili studovat interakc\u00ED mezi cisplatinou a GSH pomoc\u00ED pr\u016Ftokov\u00E9 injek\u010Dn\u00ED anal\u00FDzy s elektrochemickou detekc\u00ED (FIA-ED).Limit pro detecton GSH byla 100 pg ml-1. Z toho jasn\u011B vypl\u00FDv\u00E1 z v\u00FDsledk\u016F z\u00EDskan\u00FDch, \u017Ee optim\u00E1ln\u00ED postup je vhodn\u00E9 zkoumat interakci mezi GSH a cisplatinou. Krom\u011B toho jsme hodnotili vznik komplexu spektrometri\u00ED. V spektrometrick\u00E9 Z\u00EDskan\u00E9 v\u00FDsledky byly v dobr\u00E9 shod\u011B s t\u011Bmi electrochemical. Pot\u00E9, co jsme navrhli experiment\u00E1ln\u00ED sch\u00E9ma, kde se sm\u011Bs GSH, DNA a cisplatinou dr\u017Eeni n\u011Bkolik hodin, za ur\u010Dit\u00FDch experiment\u00E1ln\u00EDch podm\u00EDnek. V\u00FDrobky t\u00E9to interakce byl analyzov\u00E1n pomoc\u00ED r\u016Fzn\u00FDch analytick\u00FDch technik, elektrochemick\u00FD biosenzor pro detekci Pt-DNA adukty, FIA-ED analyzovat Pt-GSH komplexy a kapalinov\u00E9 chromatografie s hmotnostn\u00ED spektrometri\u00ED vyhodnotit v\u00FDsledky z\u00EDskan\u00E9 v elektrochemick\u00FDch technik."@en . "Beklov\u00E1, Miroslava" .