Inhibition of cytomegalovirus-stimulated human cell ornithine decarboxylase by α-difluoromethylornithine

Harriet C. Isom, Anthony E. Pegg

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Abstract

1. The relationship between synthesis of putrescine, human cytomegalovirus DNA synthesis, cell DNA synthesis, and human cytomegalovirus replication has been studied. 2. Stimulation of ornithine decarboxylase activity by shifting low serumarrested whole human embryo cells to high serum medium is inhibited more than 99% by 2.5 mM dl-α-difluoromethylornithine. The addition of dl-α-difluoromethylornithine to human cells arrested in low serum and subsequently stimulated by the addition of fresh high serum-containing medium, causes a greater percent inhibition of ornithine decarboxylase activity than when the drug is added to growing human cells. 3. Increased ornithine decarboxylase activity produced by infection of low serum-arrested human cells was inhibited by 5.0 mM of dl-α-difluoromethylornithine. However, at a concentration of 5.0 mM, neither dl-α-methylornithine nor dl-α-difluoromethylornithine affected human cytomegalovirus growth or was toxic to these cells. These data suggest that the increased putrescine synthesis produced by infection is not required for virus replication. 4. The addition of 5.0 mM dl-α-difluoromethylornithine had no effect on human cytomegalovirus DNA synthesis or human cytomegalovirus-induced stimulation of cell DNA synthesis. However, 5.0 mM dl-α-difluoromethylornithine significantly reduced the stimulation of cell DNA synthesis caused by treatment with mock infecting fluid.

Original languageEnglish (US)
Pages (from-to)402-413
Number of pages12
JournalBBA Section Nucleic Acids And Protein Synthesis
Volume564
Issue number3
DOIs
StatePublished - Oct 25 1979

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All Science Journal Classification (ASJC) codes

  • Medicine(all)

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