Selective inhibition of the proliferation of herpes simplex virus type 1 thymidine kinase gene-transformed murine mammary FM3A carcinoma cells by (E)-5-(2-bromovinyl)-2'-deoxyuridine and related compounds.
Mouse mammary carcinoma FM3A cells deficient in thymidine kinase were transformed by a cloned gene for herpes simplex virus type 1 thymidine kinase. Among several anti-herpetic nucleoside analogues, (E)-5-(2-bromovinyl)-2'-deoxyuridine, (E)-5-(2-iodovinyl)-2'-deoxyuridine and (E)-5-(2-bromovinyl)-2'-deoxycytidine inhibited the growth of the transformed cells at concentrations 5000- to 20000-fold lower than those required to inhibit the growth of the corresponding wild-type cells. The selective inhibitory action of these compounds was due to a specific phosphorylation by the viral thymidine kinase. From the transformed cells, thymidine-auxotrophic mutants that are deficient in thymidylate synthase were isolated. These mutant cell lines should prove useful in elucidating the mechanism of action of the antiherpetic nucleoside analogues.
D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology*; D001973:Bromodeoxyuridine / Q000031:analogs & derivatives* / Q000494:pharmacology; D002460:Cell Line; D002472:Cell Transformation, Viral / Q000187:drug effects*; D003001:Cloning, Molecular; D005796:Genes; D005814:Genes, Viral; D008325:Mammary Neoplasms, Experimental; D051379:Mice; D051381:Rats; D018139:Simplexvirus / Q000187:drug effects / Q000201:enzymology / Q000235:genetics*; D013937:Thymidine Kinase / Q000235:genetics*
D000998:Antiviral Agents; C020235:brivudine; D013937:Thymidine Kinase; D001973:Bromodeoxyuridine