Interaction of cis-diamminedichloroplatinum (II) to chromatin. Specificity of the drug distribution

Abstract

We have studied the interaction of the antitumoral drug, cis-diamminedichloroplatinum (II), cis-DDP, to chromatin. Degradation of chromatin-platinum complexes with micrococcal nuclease releases the platinum bound to the linker DNA. By comparing the percentage of platinum released throughout the digestion to the percentage of acid-soluble DNA we suggest that the linker DNA is the preferential target for this drug. This is mainly the case when the amount of bound platinum is low (r less than 0.03) and is less at higher drug concentrations. By comparing the rate constants corresponding to the reaction of cis-DDP to chromatin, DNA or core particle it appears that these constants are the same. This indicates that the bound platinum is located mainly at the DNA level. Our results are discussed with respect to the structure of chromatin and we conclude that this structure should play a role in the in vivo association of cis-DDP to DNA.