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Phosphorylation of 5-bromodeoxycytidine in cells infected with herpes simplex virus.

Abstract
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.
AuthorsG M Cooper
JournalProceedings of the National Academy of Sciences of the United States of America (Proc Natl Acad Sci U S A) Vol. 70 Issue 12 Pg. 3788-92 (Dec 1973) ISSN: 0027-8424 [Print] United States
PMID4359489 (Publication Type: Journal Article)
Chemical References
  • Bromides
  • DNA, Neoplasm
  • Deoxyribonucleosides
  • Deoxyribonucleotides
  • Deoxycytidine
  • Tritium
  • Deoxycytidine Monophosphate
  • Phosphorus
  • 5-bromodeoxycytidine 5'-monophosphate
  • DNA
  • Phosphotransferases
  • Bromodeoxyuridine
Topics
  • Adult
  • Animals
  • Bromides
  • Bromodeoxyuridine (metabolism)
  • Carcinoma
  • Carcinoma, Squamous Cell (enzymology)
  • Cell Line
  • Cell Transformation, Neoplastic
  • Cricetinae
  • DNA (biosynthesis)
  • DNA, Neoplasm (biosynthesis)
  • Deoxycytidine (metabolism)
  • Deoxycytidine Monophosphate (analogs & derivatives)
  • Deoxyribonucleosides (metabolism)
  • Deoxyribonucleotides (biosynthesis)
  • Female
  • Humans
  • Kidney
  • Laryngeal Neoplasms
  • Middle Aged
  • Phosphorus (metabolism)
  • Phosphotransferases (metabolism)
  • Simplexvirus (growth & development)
  • Tritium
  • Uterine Cervical Neoplasms (enzymology)
  • Viral Plaque Assay

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