Cis-Dichlorodiammineplatinum [II]: Inhibition of Nucleic Acid Synthesis in Lymphocytes Stimulated with Phytohemagglutinin

Abstract

cis-Dichlorodiammineplatinum (II) (cis-[Pt(NH3)2Cl2]0) is a potent and probably irreversible inhibitor of deoxyribonucleic acid synthesis in cultures of human lymphocytes stimulated with phytohemagglutinin mitogen. At low concentration (3 × 10-6M), selectivity for this process is quite evident; rates of synthesis of ribonucleic acid and protein are only slightly diminished. No resolvable cytologic lesion coincident with the action of the inhibitor was observed by electron microscopy. It was proposed that cis-[Pt(NH3)2Cl2]0 may undergo two sequential transformations, with the loss of one Cl- ion at each step, and that the resultant platinum species may act bifunctionally to cross-link adjacent nucleophilic centers through covalent binding.