{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,11]],"date-time":"2026-03-11T13:47:45Z","timestamp":1773236865856,"version":"3.50.1"},"reference-count":35,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2004,6,18]],"date-time":"2004-06-18T00:00:00Z","timestamp":1087516800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal of Medical Virology"],"published-print":{"date-parts":[[2004,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>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\u2010Barr Virus (EBV)\u2010targeted 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 \u03bcM HU for more than 2 months. EBV DNA was eliminated in about 40% of the cells in the HU\u2010treated cultures. The cells were cloned from such cultures, and only EBV\u2010positive clones could be isolated in 102 examined clones. No differences were observed in the EBV\u2010latent state, EBV\u2010gene expression, or cell growth between HU\u2010untreated Raji cells and HU\u2010treated clones. However, relative to parental Raji cells, the HU\u2010treated Raji clones were almost eight times resistant to growth inhibition by HU according to the ID<jats:sub>50<\/jats:sub> 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\u2010expression of the R2 component of RR. However, the HU\u2010resistant clones were sensitive to gemcitabine, another inhibitor of RR, and this seems highly relevant to chemotherapeutic combination in the use of these drugs. J. Med. Virol. 73:589\u2013595, 2004. \u00a9 2004 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/jmv.20130","type":"journal-article","created":{"date-parts":[[2004,6,18]],"date-time":"2004-06-18T16:04:01Z","timestamp":1087574641000},"page":"589-595","source":"Crossref","is-referenced-by-count":10,"title":["Mechanism for induction of hydroxyurea resistance and loss of latent EBV genome in hydroxyurea\u2010treated Burkitt's lymphoma cell line Raji"],"prefix":"10.1002","volume":"73","author":[{"given":"Ru","family":"Jiang","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jian\u2010Ling","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yukio","family":"Satoh","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takeshi","family":"Sairenji","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2004,6,18]]},"reference":[{"key":"e_1_2_1_2_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.72.4.1477"},{"key":"e_1_2_1_3_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/12.2.1149"},{"key":"e_1_2_1_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/bjc.1998.750"},{"key":"e_1_2_1_5_1","doi-asserted-by":"publisher","DOI":"10.1086\/515290"},{"key":"e_1_2_1_6_1","doi-asserted-by":"crossref","first-page":"1292","DOI":"10.1128\/jvi.67.3.1292-1299.1993","article-title":"Episomal and integrated copies of Epstein\u2013Barr virus coexist in Burkitt lymphoma cell lines","volume":"67","author":"Delecluse HJ","year":"1993","journal-title":"J Virol"},{"key":"e_1_2_1_7_1","first-page":"61","article-title":"Difluorodeoxyguanosine: Cytotoxicity, metabolism, and actions on DNA sythesis in human leukemia cells","volume":"22","author":"Gandhi V","year":"1995","journal-title":"Semin Oncol"},{"key":"e_1_2_1_8_1","doi-asserted-by":"crossref","first-page":"5711","DOI":"10.1016\/S0021-9258(19)83836-X","article-title":"Characterization of the free radical of mammalian ribonucleotide reductase","volume":"257","author":"Graslund A","year":"1982","journal-title":"J Biol Chem"},{"key":"e_1_2_1_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/1097-0142(19920701)70:1<185::AID-CNCR2820700129>3.0.CO;2-J"},{"key":"e_1_2_1_10_1","first-page":"29","volume-title":"Epstein\u2013Barr virus and human cancer. 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