TY - JOUR
T1 - Inhibition of cytomegalovirus-stimulated human cell ornithine decarboxylase by α-difluoromethylornithine
AU - Isom, Harriet C.
AU - Pegg, Anthony E.
N1 - Funding Information:
The authors are grateful to Dr. Fred Rapp for his interest and support and to Mr. Jay Backstrom and Mr. Timothy Hessert for excellent technical assistance. This work was supported by Contract No. N01-CP-5-3516 within the Virus Cancer Program of the National Cancer Institute and by grants CA 18450 and CA 18138 awarded by the National Cancer Institute. A.E.P. is a recipient of an established investigatorship (AHA-76-163) from the American Heart Association.
PY - 1979/10/25
Y1 - 1979/10/25
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=0018575049&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0018575049&partnerID=8YFLogxK
U2 - 10.1016/0005-2787(79)90031-5
DO - 10.1016/0005-2787(79)90031-5
M3 - Article
C2 - 227464
AN - SCOPUS:0018575049
SN - 0005-2787
VL - 564
SP - 402
EP - 413
JO - BBA Section Nucleic Acids And Protein Synthesis
JF - BBA Section Nucleic Acids And Protein Synthesis
IS - 3
ER -