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

Abstract

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[a]anthracene), nor the potent (ultimate) liver carcinogen N-acetoxy-N-2-acetylamino-fluorene induced EBV. A series of compounds, representing three classes of tumor-promoting diterpene esters (e.g., 12-O-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, 4alpha-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.

Modulation by the Polyoxotungstate HPA-23 of Epstein--Barr Virus Early Antigen Expression in Raji Cells Treated with Iododeoxyuridine

“…Indeed, the effect of HPA-23 on EA expression is quite different in cells induced with antibody to surface immunoglobulin (Tovey et al, 1978), or 12-O-tetradecanoylphorbol 13-acetate (TPA) (Zur Hausen et al, 1979), agents which probably act on the cell surface and do not require internalization. Thus, HPA-23 inhibited EA induction in Raji cells treated concomitantly with anti-/~ immunoglobulin, although pretreatment with the heteropolyanion was without effect (data not shown).…”

Anti-tumour promoter activity in Malaysian ginger rhizobia used in traditional medicine

“…Zur Hausen et al (1978Hausen et al ( , 1979 demonstrated that phorbol esters which possessed tumour-promoting activity could induce viral cycle in latently infected cells carrying EBV, and Ito et al (1981a) noted that low concentration of n-butyrate increased the effects of tumour promoters synergistically. It is noteworthy that such EBV-activating principles can be considered to possess tumour-promoting capacity (Ito et al, 1981b).…”

Interaction between latent papovavirus genomes and the tumor promoter TPA

“…Induction of Epstein-Barr virus (EBV) antigens and stimulation of particle synthesis by treatment of the EBV-carrying cell lines with TPA was reported in [ 2,3]. Here we report that TPA exclusively enhances the viral DNA content of cells which harbor papovavirus genomes in a latent episomal state.…”

“…To examine whether the tumor-promoting agent has an enhancing effect on such latent HD genomes as in the case of EBV [2,3] we have compared the viral DNA content of a number of HD containing cell lines with and without treatment with TPA. Examples of reassociation kinetic experiments are show in fig.1.…”