Mechanism for induction of hydroxyurea resistance and loss of latent EBV genome in hydroxyurea-treated Burkitt's lymphoma cell line Raji

Journal of Medical Virology
Ru JiangTakeshi Sairenji

Abstract

Hydroxyurea (HU), as an inhibitor of ribonucleotide reductase (RR) through interaction with the R2 component, has been used in the treatment of malignancies. Recently, therapeutic strategies in Epstein-Barr Virus (EBV)-targeted lymphoma have been reported. In order to study the effect of HU on EBV, infected Burkitt's lymphoma (BL) Raji cells were passaged in medium containing 50 microM HU for more than 2 months. EBV DNA was eliminated in about 40% of the cells in the HU-treated cultures. The cells were cloned from such cultures, and only EBV-positive clones could be isolated in 102 examined clones. No differences were observed in the EBV-latent state, EBV-gene expression, or cell growth between HU-untreated Raji cells and HU-treated clones. However, relative to parental Raji cells, the HU-treated Raji clones were almost eight times resistant to growth inhibition by HU according to the ID50 value, and the expression of the R2 component of RR increased more than two to three times. These results indicate that HU not only efficiently eliminates the EBV genome from Raji cells but also induces HU resistance. HU resistance was accompanied by over-expression of the R2 component of RR. However, the HU-resistant clones were sensitive to...Continue Reading

References

Apr 1, 1975·Proceedings of the National Academy of Sciences of the United States of America·A Adams, T Lindahl
Apr 15, 1975·International Journal of Cancer. Journal International Du Cancer·B M ReedmanG Klein
Jan 25, 1984·Nucleic Acids Research·M AnvretG Bjursell
Dec 1, 1995·Journal of Virology·S K Srinivas, J W Sixbey
May 21, 1998·The Journal of Infectious Diseases·J ChodoshJ W Sixbey
Aug 26, 1998·British Journal of Cancer·J Carmichael
Jan 17, 2002·Journal of Medical Virology·Yoshiko HoshikawaTakeshi Sairenji
May 1, 1965·Journal of Clinical Pathology·J V PULVERTAFT

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Citations

Aug 12, 2005·Current Opinion in Oncology·Carmen Manuela Klass, Margaret K Offermann
Dec 17, 2008·Journal of Virology·Jing ZhouPaul M Lieberman
Oct 12, 2010·Journal of Biomolecular Screening·Scott ThompsonPaul M Lieberman
Nov 26, 2008·Journal of Bacteriology·Mohube B MowaValerie Mizrahi

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