Molecular Pharmacology, Vol 19, 122-129, Copyright © 1981 by the American Society for Pharmacology and Experimental Therapeutics

Effects of E-5-(2-Bromovinyl)-2'-Deoxyuridine and Other Selective Anti-Herpes Compounds on the Induction of Retrovirus Particles in Mouse BALB/3T3 Cells

¹ Department of Human Biology, Division of Microbiology, Rega Institute for Medical Research, Katholieke Universiteit Leuven, B-3000 Leuven, Belgium

Of a large series of nucleoside analogues, all of which have proven to be effective inhibitors of herpes simplex virus replication in either cell cultures or animals (or both), only a few compounds, viz., 5-propynyloxy-2'-deoxyuridine and 5-iodo- or 5-bromo-2'-deoxyuridine and -2'-deoxycytidine were found to stimulate the release of retro ("reverse transcriptase" or RNA-directed DNA polymerase-containing)-virus particles from mouse BALB/3T3 cells. Many other nucleoside analogues, including the highly selective antiherpes agents acycloguanosine, thymine arabinoside, and E-5-(2-bromovinyl)-2'-deoxyuridine, failed to do so. Although the latter observations add further credence to the safety of acycloguanosine, thymine arabinoside, and E-5-(2-bromovinyl)-2'-deoxyuridine as antiherpes drugs, they also suggest that these compounds either are not incorporated into BALB/ 3T3 cell DNA or are incorporated to an extent that does not lead to the expression of oncornaviral genes. This possibility was directly assessed with a radiolabeled analogue of E-5-(2-bromovinyl)-2'-deoxyuridine, namely E-5-[2-¹²⁵I-vinyl]-2'-deoxyuridine. Under conditions where [5-¹²⁵I]2'-deoxyuridine was effectively incorporated into BALB/3T3 cell DNA, no such incorporation could be evidenced for E-5-[2-¹²⁵I-vinyl]-2'-deoxyuridine.

Note:
ACKNOWLEDGMENTS We thank Ms. Francine Cornette for help with the reverse transcriptase measurements; Ms. Christiane Callebaut for editorial assistance; Dr. W. H. Prusoff for advice; and our colleagues Dr. P. F. Torrence, Dr. T. Kulikowski, Dr. D. Shugar, Dr. C. L. Schmidt, Dr. M. P. Mertes, Dr. P. J. Barr, Dr. R. T. Walker, and Dr. A. S. Jones for the synthesis and supply of the test compounds.