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Stimulation of Rauscher Leukemia Virus DNA Polymerase DNA-directed DNA Synthesis by Cationic Trypanocides and Polyamines¹

Memorial Sloan-Kettering Cancer Center, New York, New York 10021 [S. L. M., J. J. B.], and Haskins Laboratories and Biology Department, Pace University, New York, New York 10038 [D. P. P., C. J. B.]

Activated DNA-directed DNA synthesis catalyzed by Rauscher leukemia virus (RLV) and other type C mammalian retroviral DNA polymerases is uniquely stimulated by biologically active polyamines. Cationic trypanocides may act as antagonists of polyamine function. As described here, several cationic trypanocides stimulate RLV polymerase-catalyzed DNA-directed DNA synthesis at concentrations significantly inhibiting eukaryotic DNA polymerases. Such stimulation is negated by polyamines. Kinetic analysis of the stimulation of RLV DNA polymerase by three structurally dissimilar cationic trypanocides (Antrycide, Burroughs-Wellcome Compound 64A, and Bayer Compound 1694) suggests that such stimulation is, in part, due to a drug:DNA structural interaction resembling the polyamine:DNA structural complex recognized by the RLV DNA polymerase.

¹ This work was supported by NIH Grant AI-17340 and National Cancer Institute Grant CA-18369.

² Present address: Bronx Municipal Hospital Center, Department of Medicine, Bronx, NY 10461.

³ To whom requests for reprints should be addressed.

Received 5/14/84. Accepted 9/21/84.