DNA-Platinum Thin Films for Use in Chemoradiation Therapy Studies

Abstract EN

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.