Synergistic inhibition of Epstein-Barr virus: transformation of B lymphocytes by alpha and gamma interferon and by 3'-azido-3'-deoxythymidine.
We analyzed the effects of 3'-azido-3'deoxythymidine (AZT) and alpha and gamma interferon (IFN-alpha and IFN-gamma) on transformation of human umbilical cord lymphocytes (HUCLs) by Epstein-Barr virus (EBV). B lymphocytic outgrowth from HUCLs infected with EBV was monitored by focus formation; the presence of EBV genomes in transformed foci was confirmed by in situ cytohybridization and EBV nuclear antigen. The 50% inhibitory doses for preventing focus formation were 0.14 microM for AZT, 10 units (U)/mL for IFN-alpha, and 1 U/mL for IFN-gamma. To determine whether inhibition resulted from direct cytotoxic effects, we assessed the viability of nontransformed HUCLs exposed to the agents for 30 d. The nontoxic doses were 1 microM for AZT, 30 U/mL for IFN-alpha, and 3 U/mL for IFN-gamma. Combining IFN-alpha or IFN-gamma with AZT or IFN-alpha with IFN-gamma at nontoxic doses showed synergistic decreases in numbers of transformed foci. Transformation of HUCLs by EBV was sensitive to, but not abolished by, these agents at doses below those required for cell killing.
Lin
J C
JC
Lineberger Cancer Research Center, School of Medicine, University of North Carolina, Chapel Hill 27514.
Zhang
Z X
ZX
Chou
T C
TC
Sim
I
I
Pagano
J S
JS
D001402:B-Lymphocytes / Q000166:cytology / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D002472:Cell Transformation, Viral / Q000187:drug effects*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004854:Herpesvirus 4, Human / Q000187:drug effects / Q000235:genetics*; D006801:Humans; D007370:Interferon Type I / Q000494:pharmacology*; D007371:Interferon-gamma / Q000494:pharmacology*; D015215:Zidovudine / Q000494:pharmacology*
D007370:Interferon Type I; D015215:Zidovudine; D007371:Interferon-gamma