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    Please use this identifier to cite or link to this item: http://ir.nhri.org.tw/handle/3990099045/5274


    Title: N-methyl-N′-nitro-N-nitrosoguanidine induces and cooperates with 12-O-tetradecanoylphorbol-1,3-acetate/sodium butyrate to enhance Epstein-Barr virus reactivation and genome instability in nasopharyngeal carcinoma cells
    Authors: Huang, SY;Fang, CY;Tsai, CH;Chang, Y;Takada, K;Hsu, TY;Chen, JY
    Contributors: National Institute of Cancer Research;Division of Infectious Diseases
    Abstract: Seroepidemiological studies implicate a correlation between Epstein-Barr virus (EBV) reactivation and the development of nasopharyngeal carcinoma (NPC). Moreover, N-nitroso compounds are known chemical carcinogens in preserved foodstuffs and cigarettes and have been implicated as risk factors contributing to the development of NPC. Here, NPC cell lines latently infected with EBV, NA and HA, and the corresponding EBV-negative NPC cell lines, NPC-TW01 and HONE-1, were used as the model system in this study. We demonstrate that the reactivation of EBV increases with increasing concentrations of N-methyl-N′-nitro-N-nitrosoguanidine (MNNG). MNNG at a single non-toxic concentration (0.1μg/ml) did not induce discernible reactivation of EBV, but repeated treatment with this concentration of MNNG significantly induced viral reactivation. Furthermore, low dose MNNG (0.1μg/ml) had a synergistic effect with 12-O-tetradecanoylphorbol-1,3-acetate (TPA)/sodium butyrate (SB) (10 ng/ml and 0.75 mM, respectively) on EBV reactivation. Through promoter activity assay, MNNG was found to enhance the transcriptional activity of Rta on Rta and Zta promoters. Using siZta to block EBV reactivation, the concomitant induction of genome instability was diminished indicating that reactivation is critical for enhancing genome instability. Co-treatment with TPA/SB and MNNG markedly increased the levels of γH2AX and ROS formation in NPC cells, which may be responsible for the increase of genome instability. Our findings offer a possible mechanism by which N-nitroso compounds induce reactivation of EBV and contribute to malignant progression by enhancing genome instability in NPC cells.
    Date: 2010-12
    Relation: Chemico-Biological Interactions. 2010 Dec;188(3):623-634.
    Link to: http://dx.doi.org/10.1016/j.cbi.2010.09.020
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=0009-2797&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000285169100030
    Cited Times(Scopus): http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=78149470136
    Appears in Collections:[陳振陽] 期刊論文
    [張堯] 期刊論文

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