The biological activity of hydrogen peroxide. III. Induction of Epstein‐Barr virus via indirect action, as compared with TPA and teleocidin

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Abstract
Hydrogen peroxide (H2O2 ) was found to be a potent inducer of the production of the early antigen complex (EA) and/or virus capsid antigen (VCA), determined by Epstein‐Barr virus (EBV). Maximum synthesis of EBV antigens was induced by 0.2 mm H2O2, 5 days after a single 10‐min treatment, in both B95‐8 cells (30.2%) and P3HR‐1 cells (17.4%). These induction frequencies by H2O2 of proteins encoded by the EBV genome were almost the same as those obtained by 10 min treatment with the potent inducers, 12‐O‐tetradecanoylphorbol‐13‐acetate (TPA) and teleocidin. In combination with n‐butyrate (4mm), H2O2 showed an additive induction of EBV antigens (1.9‐ and 1.7‐fold in B95‐8 and P3HR‐1 cells, respectively) and was as efficient as TPA and teleocidin. H2O2 induced EBV antigens at a very low level (less than 1 %) in Raji cells by itself, but it induced EBV antigens synergistically in combination with n‐butyrate (about 25‐fold). In combined treatments using H2O2, TPA and teleocidin, the combination of H2O2 and TPA or H2O2 and teleocidin showed additive effects on the induction of synthesis of EBV antigens, but the combination of TPA and teleocidin showed almost the same induction level as that produced by H2O2, TPA or teleocidin alone. The inducing activities of H2O2, TPA and teleocidin were suppressed completely, in the case of H2O2, and slightly, in the cases of TPA and teleocidin, by treatment with catalase. Moreover, the effects of H2O2 were largely suppressed by scavengers of hydroxyl radical (‐OH) and singlet oxygen (1O2), but not by superoxide dismutase (SOD), whereas the induction of EBV proteins by TPA and teleocidin was largely suppressed by SOD, but only slightly by scavengers of ‐OH and 1O2. Thus, the biological actions of H2O2 on the activation of the EBV genome seem to be essentially different from those of TPA and teleocidin, though the biological actions of TPA and teleocidin may be partially ascribed to those of H2O2.