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Bioinorg Chem Appl. 2012; 2012: 923914.
Published online Oct 2, 2011. doi:  10.1155/2012/923914
PMCID: PMC3184495
DNA-Platinum Thin Films for Use in Chemoradiation Therapy Studies
Mohammad Rezaee, * Elahe Alizadeh, Darel Hunting, and Léon Sanche
Groupe en Sciences des Radiations, Départment de Médecine Nucléaire et Radiobiologie, Faculté de Médecine et des Sciences de la Santé, Université de Sherbrooke, Sherbrooke, QC, Canada J1H5N4
*Mohammad Rezaee: mohammad.rezaee/at/usherbrooke.ca
Academic Editor: Goran N. Kaluderovic
Received July 8, 2011; Accepted August 3, 2011.
Abstract
Dry films of platinum chemotherapeutic drugs covalently bound to plasmid DNA (Pt-DNA) represent a useful experimental model to investigate direct effects of radiation on DNA in close proximity to platinum chemotherapeutic agents, a situation of considerable relevance to understand the mechanisms underlying concomitant chemoradiation therapy. In the present paper we determine the optimum conditions for preparation of Pt-DNA films for use in irradiation experiments. Incubation conditions for DNA platination reactions have a substantial effect on the structure of Pt-DNA in the films. The quantity of Pt bound to DNA as a function of incubation time and temperature is measured by inductively coupled plasma mass spectroscopy. Our experiments indicate that chemical instability and damage to DNA in Pt-DNA samples increase when DNA platination occurs at 37°C for 24 hours, the condition which has been extensively used for in vitro studies. Platination of DNA for the formation of Pt-DNA films is optimal at room temperature for reaction times less than 2 hours. By increasing the concentration of Pt compounds relative to DNA and thus accelerating the rate of their mutual binding, it is possible to prepare Pt-DNA samples containing known concentrations of Pt while reducing DNA degradation caused by more lengthy procedures.
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