DNA-Protein Crosslinking of Platinum Coordination Complex in Living Cells: Implication to Evaluate the Cytotoxic Effects of Chemotherapeutic Agents
The first report by Rosenberg et al. (1) that, out of several platinum coordination complexes, the cis-diamminedichloroplatinum (II), (or cis-DDP) was most effective in inhibiting the growth of sarcoma 180 in mice has initiated intensive research into its mode of biological action, especially since its isomer, the trans-DDP, is essentially inactive (2,3). Because both isomers have been shown to bind DNA, it must be the stereospecificity of this binding which sets them apart as antitumor agents. Indeed, the elegant experiments of Lippard and his associates (4), who developed antibodies specific for intrastrand crosslinks of two adjacent guanine residues, showed that only cis-DDP was capabable of binding to the DNA in this fashion. The trans-isomer did not produce detectable crosslinks of this kind. These findings, supported by x-ray crystallography (5), together with the reports of others (6), suggest that the intrastrand DNA crosslinking by cis-DDP may be responsible tor its antitumor activity.
KeywordsHeLa Cell Nuclear Matrix HeLa Nucleus Alkaline Elution Intrastrand Cross Link
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