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Inhibition of Mammalian DNA Polymerases by Recombinant -Interferon and -Interferon¹

Hematological Disease Center, Nagoya National Hospital, Naka-ku [M. T., K. K.], and Institute for Disease Mechanism and Control, Nagoya University School of Medicine [S. Y.] Nagoya, Japan

Interferons (IFNs) have been shown to suppress the growth of both normal and malignant cells. We examined the effect of gene-cloned IFN- and IFN- on the in vitro activities of human, calf, or rat DNA polymerases. IFN- strongly inhibited the reactions of DNA polymerase and ß at apparent K_i values of 1.25 and 0.35 x 10⁵ antiviral units/ml, respectively, but inhibited DNA polymerase only slightly. IFN- inhibited the reaction of DNA polymerase more strongly (K_i, 1.2 x 10⁴ units/ml) than IFN-, but not that of DNA polymerase ß. On the other hand, neither IFN- nor IFN- inhibited the reactions of DNA polymerase I from Escherichia coli, Klenow fragment, T-4 DNA polymerase, and RNA polymerase. The fact that K_i values for IFN- of DNA polymerase from calf thymus, human leukemic cells, and rat liver were similar suggests the absence of species specificity among animals with regard to the inhibition of DNA polymerases by IFNs. These results indicate that DNA polymerase may be one of the targets of the action of IFNs.

¹ This work was supported in part by a Grant-in-Aid for Cancer Research from the Ministry of Health and Welfare of Japan.

² To whom requests for reprints should be addressed.

Received 12/17/86. Revised 6/ 5/87. Accepted 8/14/87.

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