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Comparative Inhibition of Purified DNA Polymerases from Murine Leukemia Virus and Human Lymphocytes by 1-ß-D-Arabinofuranosylcytosine 5'-Triphosphate

Drug Research and Development [A. W. S.], and Laboratory of Tumor Cell Biology [R. G. S., R. C. G.], National Cancer Institute, NIH, Bethesda, Maryland 20014

The K_m for dCTP and the K₁ for 1-ß-D-arabinofuranosylcytosine 5'-triphosphate (ara-CTP) were determined with DNA polymerases purified by diethylaminoethyl cellulose and phosphocellulose chromatography from Rauscher murine leukemia virus, from human blood lymphocytes, and from a human lymphoblastoid cell line. Inhibition of the viral reverse transcriptase varied with the template/primer used. With poly(rI)·oligo(dC) (rI_n·dC_12-18) as the synthetic template/primer, this enzyme had a greater relative affinity for the inhibitor than had the cellular enzymes in the presence of DNA. However, when DNA was the template, inhibition of the viral enzyme was decreased considerably. DNA polymerase I of normal human lymphoid cells, which was separated from the lowermolecular-weight polymerase II and could be assayed only in the presence of DNA, had a lower relative affinity for ara-CTP than the viral reverse transcriptase directed by poly(rI)·oligo(dC). However, in the presence of magnesium ions and a DNA template, the viral enzyme was inhibited far less than either of the cellular enzymes. Since ara-CTP inhibits both viral and cellular DNA polymerases and inhibition varies with the template used, the compound cannot be considered a specific inhibitor of reverse transcriptase in studies of virus-cell interactions. The suggestion that polymerase I is involved in DNA replication is consistent with the finding that, in the presence of "activated" DNA, it is inhibited to a greater extent by ara-CTP than is polymerase II.

¹ To whom reprint requests should be addressed, at Room 6N-119, Building 10, National Cancer Institute, NIH, Bethesda, Md. 20014.

Received 5/11/73. Accepted 10/25/73.