Biochemistry 1990, 29, 8461-8466 Wilson, W. D., Tanious, F. A., Watson, R., Barton, H. J., Strekowska, A., Harden, D. B., & Strekowski, L. (1989b) Biochemistry 28, 1984-1992. Wilson, W. D., Tanious, F. A., Barton, H. J., Wydra, R. L.,
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Effect of the Antitumor Drug cis-Diamminedichloroplatinum( 11) and Related Platinum Complexes on Eukaryotic DNA Replication+ Wendy J. Heiger-Bernays,bg John M. Essigmann,****gand Stephen J. Lippard*,$ Department of Chemistry and Whitaker College of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139 Received April 20, 1990
An SV40-based in vitro replication system has been used to examine the effects of platinum compounds on eukaryotic D N A replication. Plasmid templates containing the SV40 origin of replication were modified with the anticancer drug cis-diamminedichloroplatinum(I1) (cis-DDP, cisplatin) or the inactive analogues [Pt(dien)Cl]+ and trans-DDP. The platinated plasmids were used as templates for DNA synthesis by the DNA polymerases present in cytosolic extracts prepared from human cell lines HeLa and 293. Bifunctional adducts formed by cis- and trans-DDP inhibited D N A replication by 95% at a bound drug to nucleotide ratio [(D/N)b] of
