Book of Abstracts: Albany 2009
June 16-20 2009
© Adenine Press (2008)
The Effect of UV radiation on DNA-cis-DDP Complex
The current work was carried out to investigate the cooperative effects of UV radiation and cis-DDP (cis-diamminedichloroplatinum) on DNA helix-coil transition thermodynamics. The antineoplastic agent cis-DDP has been used to successfully treat tumors since 1978, nevertheless there is little known about the nature of cis-DDP?s interaction with nucleic acids. Cis-DDP has stabilizing effects on DNA double helix within the relative concentrations on cis-DDP and DNA which result in specific interactions with GC rich blocks on DNA. Higher concentrations destabilize the DNA double helix due to the saturation of DNA with cis-DDP. This results in overall weakening of base pair interactions at the sites of cis-DDP binding to DNA due to the mechanical strain on DNA backbone. Microcalorimetric studies have shown that the complete effects of cis-DDP on DNA stability are achieved within 48 hours after treating DNA with cis-DDP at 4°C; after this, no significant changes are observed. UV radiation of cis-DDP-DNA solution reverses the stabilizing effects of cis-DDP, which are comparable to that of untreated DNA solution. In order to confirm that the reversal of cis-DDP?s stabilization of DNA under UV radiation is due to the cis-DDP-DNA complex dissociation, the irradiated cis-DDP-DNA complex was left for over 120 minutes to equilibrate. Equilibration of the irradiated complex results in the recovery of considerable fraction of the stabilization properties of cis-DDP on DNA double helix.
Yerevan State University, Faculty of physics