Molecular Pharmacology, Vol 4, 139-146, Copyright © 1968 by the American Society for Pharmacology and Experimental Therapeutics

Effect of 1--D-Arabinofuranosylcytosine on DNA Synthesis

II. In Rabbit Kidney Cells Infected with Herpes Viruses

¹ Department of Microbiology, Research Laboratories, Albert Einstein Medical Center, Philadelphia, Pennsylvania 1941

1--D-Arabinofuranosylcytosine (Ara-C) inhibits the synthesis of DNA in noninfected rabbit kidney cells to a greater degree than in cells infected with viruses of the herpes group (herpes simplex and pseudorabies viruses). Virus multiplication is inhibited by the drug to the same extent as DNA synthesis, demonstrating that Ara-C interferes with the infective process by inhibiting the synthesis of DNA only.

The relative resistance of infected cells to the action of the drug is probably due to the lower ability of these cells as compared to noninfected cells to phosphorylate Ara-C. The low level of phosphorylation of the drug in the infected cells is correlated with a decrease in the activity of deoxycytidine kinase in vivo. Furthermore, the drug does not induce in the infected cells an increase in the level of activity of deoxycytidine kinase, an effect it does produce in noninfected cells. It is concluded that Ara-C is not a specific antiviral agent.

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ACKNOWLEDGMENTS This investigation was supported by grants from the National Institutes of Health (AI-03362) and from the National Science Foundation (GB-4995), and by a U.S. Public Health Research Career Program Award (5-K3-AI-l9,335) from the National Institute of Allergy and Infectious Diseases.