Inhibition of 12-O-tetradecanoylphorbol-13-acetate-induced induction of Epstein-Barr virus early antigen in Raji cells by some inhibitors of tumor promotion.

The effects of some compounds, which have been reported to inhibit tumor promotion in vivo, on the induction of the early antigen (EA) of Epstein-Barr virus (EBV) by 12-O-tetradecanoylphorbol-13-acetate (TPA) in Raji cells were examined. The inhibitors of the cascade process involving arachidonic acid, indomethacin, nordihydroguaiaretic acid, phenidone and p-bromophenacyl bromide, effectively inhibited EBV-EA induction by TPA. Two flavonoids, morin and kaempferol also inhibited EA induction. Among antioxidants, butylated hydroxytoluene effectively inhibited EA induction, though alpha-tocopherol did not show any inhibition of EA induction at concentrations of up to 150 micrograms/ml. N-(6-Aminohexyl)-5-chloro-1-naphthalenesulfonamide, a calmodulin antagonist, and esculetin showed inhibitory effects on EA induction, though slight cytotoxicity was observed. L-1-p-Tosylamino-2-phenylethyl chloromethyl ketone, a protease inhibitor, showed cytotoxicity and no specific inhibition of EA induction. Five kinds of steroids, cortisone, hydrocortisone, prednisolone, dexamethasone and fluocinolone acetonide showed no inhibitory effect on EA induction at concentrations of up to 100 micrograms/ml. In addition, the relationship between the inhibition of EBV-EA induction and that of tumor promotion is discussed.