Murine mammary FM3A carcinoma cells transformed with the herpes simplex virus type 1 thymidine kinase gene are highly sensitive to the growth-inhibitory properties of (E)-5-(2-bromovinyl)-2'-deoxyuridine and related compounds.
Murine mammary carcinoma (FM3A TK-/HSV-1 TK+) cells, which are thymidine kinase (TK)-deficient but have been transformed with the herpes simplex virus type 1 (HSV-1) TK gene are inhibited in their growth by (E)-5-(2-bromovinyl)-2'-deoxyuridine (BVDU), (E)-5-(2-iodovinyl)-2'-deoxyuridine (IVDU) and (E)-5-(2-bromovinyl)-2'-deoxycytidine (BVDC) at 0.5, 0.5 and 0.8 ng/ml, respectively; i.e., a concentration 5000 to 20 000-fold lower than that required to inhibit the growth of the corresponding wild-type FM3A/0 cells. Hence, transformation of tumor cells with the HSV-1 TK gene makes them particularly sensitive to the cytostatic action of BVDU and related compounds.
Balzarini
J
J
de Clercq
E
E
Ayusawa
D
D
Seno
T
T
D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology; D001972:Bromodeoxycytidine / Q000031:analogs & derivatives / Q000494:pharmacology; D001973:Bromodeoxyuridine / Q000031:analogs & derivatives* / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D005260:Female; D005814:Genes, Viral; D007065:Idoxuridine / Q000031:analogs & derivatives / Q000494:pharmacology; D008325:Mammary Neoplasms, Experimental / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D051379:Mice; D008809:Mice, Inbred C3H; D010766:Phosphorylation; D018139:Simplexvirus / Q000201:enzymology* / Q000235:genetics; D013937:Thymidine Kinase / Q000235:genetics* / Q000378:metabolism; D014170:Transformation, Genetic
D000998:Antiviral Agents; D001972:Bromodeoxycytidine; C020235:brivudine; C030360:5-(2-iodovinyl)-2'-deoxyuridine; C045536:5-(2-bromovinyl)-2'-deoxycytidine; D013937:Thymidine Kinase; D001973:Bromodeoxyuridine; D007065:Idoxuridine