Chemical inducers of differentiation in Friend leukaemia cells inhibit lymphocyte mitogenesis

Abstract

Several phorbol esters, the potent tumour-promoting agents isolated from croton oil, induce proliferation of human lymphocytes and enhance the mitogenic effect of lectins on bovine lymphocytes. While studying the mitogenic properties of one of these agents, phorbol myristate acetate (PMA), we found that dimethyl sulphoxide (DMSO), frequently used as a solvent for PMA, markedly inhibits PMA-induced mitogenesis at DMSO concentrations that have little effect on phytohaemagglutinin (PHA)-induced responses. DMSO, as well as a variety of other organic compounds, induce erythroid differentiation in Friend leukaemia (FL) cells. Phorbol esters, on the other hand, are potent inhibitors of both spontaneous and induced cellular differentiation. We therefore investigated the relationship between the potency of compounds to induce erythroid differentiation in FL cells and their potency to inhibit lymphocyte proliferation induced by PMA and other mitogens. We report here that many of the compounds that induce erythroid differentiation in FL cells are similar to DMSO in selectively suppressing PMA-induced lymphocyte mitogenesis.