Interaction of deoxyribonucleic acid with cis-platinum:: Structure-activity relationship

The discovery of the cytostatic effects of cis-platinum led to more thorougoing studies concerning the chemical structure-biological activity relationship. Results of our studies presented in this paper reveal predilectly the mechanisms of interaction of cis-platinum (cDDP) with deoxyribonucleic acid (DNA) and their effects in vivo and in vitro, Investigations were performed in vitro by means of circular dichroism (CD) with respect to the interaction of cDDP with DNA and in vivo by experiments on laboratory animals concerning the effects of cDDP on hepatic DNA biosynthesis and on serumproteins. In vitro investigations, based on studies by CD, followed the evolution of cDDP / DNA systems at the wavelenght lambda =220-320 nm. The evaluation of dichroic spectra evidenced modifications in B-DNA (native form) with tendency to A-DNA and C-DNA forms. The modifications revealed a tendency to generate DNA-cDDP adducts. In vivo experiments, performed on Wistar strain rats showed, after the i.p. injection of cDDP (in physiological saline) in doses: 5, 10 amd 15 mg / body weight, the depression of hepatic DNA synthesis (with -0.04; -0.09 and -0.15 as compared with the values obtained in the case of control groups). A reverse relationship was observed between the administered dose of cDDP and the quantum of hepatic DNA. Serumproteins revealed a decrease in experimental groups reverse proportional with the administered cDDP doses.