Abstract

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.