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Blood, 1 July 2005, Vol. 106, No. 1, pp. 235-240. Prepublished online as a Blood First Edition Paper on March 24, 2005; DOI 10.1182/blood-2004-09-3748. This Article Full Text (PDF) All Versions of this Article: 2004-09-3748v1 106/1/235    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Kurokawa, M. Articles by Harrington, Jr., W. J Search for Related Content PubMed PubMed Citation Articles by Kurokawa, M. Articles by Harrington, Jr., W. J Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted September 27, 2004 Accepted February 25, 2005 Azidothymidine inhibits NF-B and induces Epstein-Barr virus gene expression in Burkitt lymphoma Motoki Kurokawa, Subrata K Ghosh, Juan C Ramos, Abdul M Mian, Ngoc L Toomey, Lisa Cabral, Denise Whitby, Glen N Barber, Dirk P Dittmer, and William J Harrington, Jr.* Department of Dermatology, Medical College, University of Miyazaki, Miyazaki, Japan Department of Medicine, University of Miami School of Medicine, Miami, FL, USA Viral Epidemiology Section, AIDS Vaccine Program, SAIC-Frederick, National Cancer Institute, Frederick, MD, USA Department of Microbiology and Immunology, University of Miami School of Medicine, Miami, FL, USA Department of Microbiology and Immunology, The University of North Carolina, Chapel Hill, NC, USA * Corresponding author; email: wharring{at}med.miami.edu. The antiviral Azidothymidine (AZT), alone or in combination with other agents, induces apoptosis in early passage Epstein Barr Virus positive Burkitt lymphoma (EBV+ BL) lines and has clinical activity in EBV+ BL. We report here a mechanism of AZT's anti-tumor activity. The nucleus of these cells contains activated NF-B subunits p50, c-Rel, RelB, and p52, but not p65. Treatment of primary EBV+ BL lines with AZT inhibited NF-B within one to two hours. This was followed by upregulation of EBV gene expression including viral thymidine kinase (vTK) and apoptosis. Subclones of EBV+ BL cells that demonstrated activated p65 were resistant to AZT. In EBV+ BLs, AZT but not Ganciclovir (GCV), was highly phosphorylated to its monophosphate form (AZT-MP). Phosphorylation, as well as apoptosis, was markedly enhanced in the presence of hydroxyurea. AZT inhibits NF-B and upregulates EBV gene expression in primary EBV+ BLs. AZT with hydroxyurea may represent an inexpensive, targeted regimen for endemic BL. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: F.-Z. Wang, D. Roy, E. Gershburg, C. B. Whitehurst, D. P. Dittmer, and J. S. Pagano Maribavir Inhibits Epstein-Barr Virus Transcription in Addition to Viral DNA Replication J. Virol., December 1, 2009; 83(23): 12108 - 12117. [Abstract] [Full Text] [PDF] Z. Han, D. Verma, C. Hilscher, D. P. Dittmer, and S. Swaminathan General and Target-Specific RNA Binding Properties of Epstein-Barr Virus SM Posttranscriptional Regulatory Protein J. Virol., November 15, 2009; 83(22): 11635 - 11644. [Abstract] [Full Text] [PDF] M. L. Gulley and W. Tang Laboratory Assays for Epstein-Barr Virus-Related Disease J. Mol. Diagn., July 1, 2008; 10(4): 279 - 292. [Abstract] [Full Text] [PDF] T. Xia, A. O'Hara, I. Araujo, J. Barreto, E. Carvalho, J. B. Sapucaia, J. C. Ramos, E. Luz, C. Pedroso, M. 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