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Suramin Affects DNA Synthesis in HeLa Cells by Inhibition of DNA Polymerases¹

Department of Biochemistry, University of Nebraska Medical Center, Omaha, Nebraska 68198-4525

Suramin, a polysulfonated naphthylurea widely used in the treatment of trypanosomiasis and onchocerciasis, is currently being investigated as an antitumor agent for the treatment of advanced cancer. Suramin exerts a wide variety of biological effects. We have shown that suramin inhibits cell proliferation and DNA synthesis in cultured HeLa cells. The replication in vitro of SV40 DNA is completely abolished by 40 µM suramin. The inhibition of DNA replication is due to inhibition of DNA polymerases and , the replicative enzymes in eukaryotic cells. DNA polymerase is sensitive to lower concentrations of suramin [concentration to achieve 50% inhibition (IC₅₀) of 8 µM] than is DNA polymerase (IC₅₀ 36 µM), whereas DNA polymerase ß is relatively insensitive to the drug (IC₅₀ of 90 µM). Suramin inhibits other replicative DNA polymerases such as Escherichia coli polymerase I (Klenow fragment) and Thermus aquaticus polymerase. Suramin is noncompetitive with both substrate deoxyribonucleotides and template-primers with respect to DNA polymerase inhibition. Much lower concentrations (8–30 µM) of the drug are required for 50% inhibition of DNA polymerases than for 50% inhibition of other enzymes such as protein kinase C and reverse transcriptase. These results show an important biological effect of this drug and indicate the need for more studies before its clinical use as an antitumor agent.

¹ This study was supported by grants to Dr. J. K. Vishwanatha from the Leukemia Research Foundation, Inc., and the Nebraska Cancer and Smoking Diseases Program.

² To whom requests for reprints should be addressed, at Department of Biochemistry, University of Nebraska Medical Center, 600 South 42nd Street, Omaha, NE 68198-4525.

Received 7/26/90. Accepted 9/18/90.

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