Opposite effects of recombinant interferon-alpha A and deoxycoformycin on adenosine deaminase activity in the Daudi B lymphoblastoid cell line.
Interferon-alpha and the adenosine deaminase (ADA) inhibitor deoxycoformycin (dCF) have each been shown to be efficacious in the treatment of some lymphoid malignancies and to have potent antiproliferative activities in vitro. This study examined whether dCF and recombinant interferon-alpha A (rIFN-alpha A) were additive, synergistic, or antagonistic in their effects on the cultured B lymphoblastoid cell line Daudi. Treatment of Daudi cells for three to four days with doses of rIFN-alpha A that were growth inhibitory was unexpectedly found to increase the level of ADA activity per cell two- to threefold and therefore to prevent the inhibition of ADA by limiting concentrations of dCF. However, the opposite effects of dCF and rIFN-alpha A on ADA activity did not lead to antagonistic effects on growth inhibition. The higher concentrations of dCF (with deoxyadenosine) necessary for appreciable growth inhibition could inhibit the increased ADA activity in rIFN-alpha A-treated cells, thus resulting in additive antiproliferative effects.
Faltynek
C R
CR
Program Resources, Inc., Frederick Cancer Research Facility, MD 21701.
D000243:Adenosine Deaminase / Q000378:metabolism*; D058892:Adenosine Deaminase Inhibitors; D001402:B-Lymphocytes / Q000187:drug effects / Q000201:enzymology*; D002051:Burkitt Lymphoma / Q000201:enzymology / Q000473:pathology*; D002455:Cell Division / Q000187:drug effects; D003070:Coformycin / Q000031:analogs & derivatives / Q000494:pharmacology*; D003839:Deoxyadenosines / Q000494:pharmacology; D004347:Drug Interactions; D006801:Humans; D007370:Interferon Type I / Q000494:pharmacology*; D008297:Male; D009363:Neoplasm Proteins / Q000378:metabolism; D009700:Nucleoside Deaminases / Q000378:metabolism*; D015649:Pentostatin; D011994:Recombinant Proteins / Q000494:pharmacology; D012263:Ribonucleosides / Q000494:pharmacology*; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000201:enzymology*
D058892:Adenosine Deaminase Inhibitors; D003839:Deoxyadenosines; D007370:Interferon Type I; D009363:Neoplasm Proteins; D011994:Recombinant Proteins; D012263:Ribonucleosides; D003070:Coformycin; D015649:Pentostatin; D009700:Nucleoside Deaminases; D000243:Adenosine Deaminase