The effect of cis-platin analogues derived from aminoalkylaminoanthraquinones on DNA cleavage: an electron microscopy study

The effects of cis -diamminedichloroplatinum(II) ( cis -DDP) and a new analog ( cis -DANAP) derived from aminoalkylaminoanthraquinones (RNH(CH 2 ) 3 NH 2 ) 2 PtCl 2 , R = anthraquinone on the oligonucleotide poly(dG)·poly(dC) were studied by electron microscopy. It was observed that with cis -DANAP, the extent of small fragments increased with the increase of the drug/nucleotide molar ratio (Rb) . This effect was not observed with cis -DDP and with the parent aminoalkylaminoanthraquinone free base. The effect was not time dependent and could be observed only at Rb > 0.4. Explanation for this phenomenon was given on the basis of monoadduct formation between the platinum and purine/pyrimidine bases which leads to strand degradation. A salt effect on the length of poly(dG)·poly(dC) is also present.