D 2006

Study of nucleic acids interactions with platinum based cytostatics using biosensor

PETRLOVÁ, Jitka, Richard PRŮŠA, Bernd SURES, Vojtěch ADAM, Ladislav ZEMAN et. al.

Basic information

Original name

Study of nucleic acids interactions with platinum based cytostatics using biosensor

Name in Czech

Studium interakcí nukleových kyselin a platinových cytostatik s použitím biosenzoru

Authors

PETRLOVÁ, Jitka (203 Czech Republic), Richard PRŮŠA (203 Czech Republic), Bernd SURES (276 Germany), Vojtěch ADAM (203 Czech Republic), Ladislav ZEMAN (203 Czech Republic), Libuše TRNKOVÁ (203 Czech Republic, guarantor) and René KIZEK (203 Czech Republic)

Edition

první. Bordeaux, 11th International conference on electroanalysis, p. 7-7, 1 pp. 2006

Publisher

European Society for ElectroAnalytical Chemistry

Other information

Language

English

Type of outcome

Stať ve sborníku

Field of Study

10405 Electrochemistry

Country of publisher

France

Confidentiality degree

není předmětem státního či obchodního tajemství

RIV identification code

RIV/00216224:14310/06:00020012

Organization unit

Faculty of Science

Keywords in English

Platinum based cytostatic drugs; nucleic acids; biosensor; electrochemistry; interaction DNA;
Změněno: 20/6/2008 12:47, prof. RNDr. Libuše Trnková, CSc.

Abstract

V originále

Introduction. 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 cisplatin mechanism of action is that the drug induces its cytotoxic properties through binding to the nuclear DNA and subsequent interference with normal transcription, and/or DNA replication mechanisms. Objective. The aim of this paper was to study of binding of platinum cytostatic to DNA structure using of platinum biosensor. Materials and methods. Preparation of DNA adduct with cisplatin. dsDNA was modified in the presence NaClO4 by cisplatin for in the dark of a thermostatic box. Purification of DNA adduct. The obtained DNA adduct was purified by ultrafiltration. Preparation of biosensor. Metallothionein modified surface of hanging mercury drop electrode was used as a platinum biosensor. The platinum and Pt-DNA adduct were detected by adsorptive transfer stripping (AdTS) differential pulse voltammetry (DPV). AdTS DPV parameters: time of accumulation 240 s, time of interaction 400 s. Results. Here we studied a binding of different platinum based cytostatics (cisplatin, carboplatin and oxaliplatin) to genome DNA. The influence of concentration of DNA, temperature and ionic strength on yield of adducts has been described. Consequently, we used the suggested heavy metal biosensor to detection of platinum modified DNA. We found out that the highest yield of Pt-DNA adducts has been obtained, if we used 100 mg/ml DNA at temperature 37 C for 24 h, because the yield of the modification was very low up to 10 h. In addition, increasing ionic strength negatively influenced yield of the modification. We were able to analyse tens of nanograms of Pt-DNA adduct per millilitre using the biosensor. Conclusions. The suggested approach shows the possible way for simple, sensitive, and rapid detection and determination of cisplatin and Pt-DNA adducts. In addition, the biosensor could be applied to study of binding of platinum to DNA structure.

In Czech

Studium interakcí nukleových kyselin a platinových cytostatik s použitím biosenzoru

Links

GP525/04/P132, research and development project
Name: Studium obranných mechanismů rostlin při stresu způsobeném těžkými kovy
MSM0021622412, plan (intention)
Name: Interakce mezi chemickými látkami, prostředím a biologickými systémy a jejich důsledky na globální, regionální a lokální úrovni (INCHEMBIOL) (Acronym: INCHEMBIOL)
Investor: Ministry of Education, Youth and Sports of the CR, Interactions among the chemicals, environment and biological systems and their consequences on the global, regional and local scales (INCHEMBIOL)