Tumour-promoting phorbol esters inhibit DNA synthesis and enhance virus-induced interferon production in a human lymphoma cell line.

12-O-tetradecanoyl-phorbol-13-acetate (TPA), a potent tumour promoter, was tested for its effects on the proliferation of the human Burkitt lymphoma cell line, Namalwa, and the synthesis of interferon by these cells. At nanomolar concentrations, TPA blocked thymidine incorporation into cellular DNA by more than 90% within 24 h. TPA-treated cells produced about 20-fold more interferon in response to Sendai virus than did untreated controls and simultaneous treatment with TPA and sodium n-butyrate gave a further two- to three-fold enhancement. Neither of these effects of TPA was reversed on removal of the compound; furthermore, exposure of Namalwa cells to TPA for only 1 h was sufficient for full activity. 4-O-methyl-TPA, a compound only marginally active as a tumour promoter, showed effects similar to TPA, but only at concentrations 300-fold higher. In contrast to its effects on Namalwa cells, TPA did not affect synthesis of interferon in response to Sendai virus in two other Burkitt lymphoma lines (Raji and Daudi) nor in the Epstein-Barr virus (EBV)-negative lymphoma line, BJAB; it inhibited interferon production in the human myeloid cell line, HL-60.