Tumor initiators and promoters in the induction of Epstein—Barr virus

DOI Web Site 被引用文献10件
  • Harald zur Hausen
    Institut für Virologie, Zentrum für Hygiene, Universität Freiburg, Hermann-Herder-Strasse 11, 7800 Freiburg, Federal Republic of Germany
  • Georg W. Bornkamm
    Institut für Virologie, Zentrum für Hygiene, Universität Freiburg, Hermann-Herder-Strasse 11, 7800 Freiburg, Federal Republic of Germany
  • Rainer Schmidt
    Deutsches Krebsforschungszentrum, Institut für Biochemie, Im Neuenheimer Feld 280, 6900 Heidelberg, Federal Republic of Germany
  • Erich Hecker
    Deutsches Krebsforschungszentrum, Institut für Biochemie, Im Neuenheimer Feld 280, 6900 Heidelberg, Federal Republic of Germany

抄録

<jats:p> The effect of various tumor initiators and promoters on induction of persisting Epstein-Barr virus (EBV) in different lines of lymphoblastoid cells was analyzed. Neither five polycyclic aromatic hydrocarbons, amongst them potent tumor initiators (e.g., 7,12-dimethylbenz[ <jats:italic>a</jats:italic> ]anthracene), nor the potent (ultimate) liver carcinogen <jats:italic>N</jats:italic> -acetoxy- <jats:italic>N</jats:italic> -2-acetylamino-fluorene induced EBV. A series of compounds, representing three classes of tumor-promoting diterpene esters (e.g., 12- <jats:italic>O</jats:italic> -tetradecanoylphorbol-13-acetate), efficiently induced EBV in persistently infected cells. The concentration required for maximal induction ranged between 0.5 and 100 nM. Some nonpromoting diterpenes (phorbol, 4α-phorbol-12,13-didecanoate, and ingenol) did not induce EBV. However, the nonpromoters, resiniferatoxin and 12-deoxyphorbol-13-decatrienoate, were effective, whereas anthralin, a tumor promoter, did not induce EBV. In three lines of EBV genome-carrying cells (Raji, NC-37, and RPMI 64-10) only abortive induction was noted, leading exclusively to synthesis of early antigen. In cells of lines with low spontaneous virus release (P3HR-1, B95-8, and QIMR-Wil), upon treatment with tetradecanoylphorbol acetate, approximately 20-40 times more viral DNA was recovered as compared to untreated controls. Viral DNA from tetradeca-noylphorbol acetate-induced cultures revealed the same restriction endonuclease cleavage pattern as viral DNA obtained from noninduced cells. Within 10 days after induction, release of infectious virus increased approximately by one order of magnitude. Prostaglandins, reported to be released after treatment with tumor promoters, were ineffective in virus induction under the conditions tested. </jats:p>

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