Phosphorylation of 5-bromodeoxycytidine in cells infected with herpes simplex virus.
5-Bromodeoxycytidine is phosphorylated to 5-bromodeoxycytidine 5'-monophosphate in extracts of cells infected with herpes simplex virus but not in extracts of uninfected cells. The conversion of 5-bromodeoxycytidine to nucleotides and its utilization for DNA synthesis in uninfected cells occurs by deamination of 5-bromodeoxycytidine to 5-bromodeoxyuridine followed by phosphorylation of 5-bromodeoxyuridine to 5-bromodeoxyuridine 5'-monophosphate. In contrast, in cells infected with herpes simplex virus, 5-bromodeoxycytidine is phosphorylated directly to 5-bromodeoxycytidine 5'-monophosphate, which can then be deaminated to 5-bromodeoxyuridine 5'-monophosphate and incorporated into DNA. These results indicate a difference in the substrate specificity of nucleoside kinases induced by herpes simplex virus and the enzymes present in uninfected cells. It is suggested that this difference in substrate specificity between virus-induced and host-cell enzymes may allow selective chemotherapy of herpes simplex infections with 5-bromo- or 5-iododeoxycytidine.
D000328:Adult; D000818:Animals; D001965:Bromides; D001973:Bromodeoxyuridine / Q000378:metabolism; D002277:Carcinoma; D002294:Carcinoma, Squamous Cell / Q000201:enzymology; D002460:Cell Line; D002471:Cell Transformation, Neoplastic; D006224:Cricetinae; D004247:DNA / Q000096:biosynthesis; D004273:DNA, Neoplasm / Q000096:biosynthesis; D003841:Deoxycytidine / Q000378:metabolism; D003843:Deoxycytidine Monophosphate / Q000031:analogs & derivatives; D003853:Deoxyribonucleosides / Q000378:metabolism*; D003854:Deoxyribonucleotides / Q000096:biosynthesis*; D005260:Female; D006801:Humans; D007668:Kidney; D007822:Laryngeal Neoplasms; D008875:Middle Aged; D010758:Phosphorus / Q000378:metabolism; D010770:Phosphotransferases / Q000378:metabolism; D018139:Simplexvirus / Q000254:growth & development*; D014316:Tritium; D002583:Uterine Cervical Neoplasms / Q000201:enzymology; D010948:Viral Plaque Assay
D001965:Bromides; D004273:DNA, Neoplasm; D003853:Deoxyribonucleosides; D003854:Deoxyribonucleotides; D003841:Deoxycytidine; D014316:Tritium; D003843:Deoxycytidine Monophosphate; D010758:Phosphorus; C006814:5-bromodeoxycytidine 5'-monophosphate; D004247:DNA; D010770:Phosphotransferases; D001973:Bromodeoxyuridine