A new class of inhibitors of lymphocyte mitogenesis: agents that induce erythroid differentiation in Friend leukemia cells.

Addition of the polar organic compounds, dimethylsulfoxide, N,N-dimethylformamide, N,N-dimethylacetamide, and butyric acid, to human lymphocyte cultures stimulated with the tumor-promoting agent, phorbol myristate acetate, results in greater than 90% inhibition of lymphocyte proliferation. Inhibition is achieved at concentrations of the organic compounds reported to be optimal for induction of erythroid differentiation in Friend leukemia cells. Butyric acid is the most potent compound tested. Compounds that are structurally related to butyric acid, but that do not induce erythroid differentiation, do not inhibit lymphocyte mitogenesis. Lymphocyte responses to other mitogens are also suppressed by the polar organic compounds, although higher concentrations are required. These agents are much less inhibitory when added 24 hr after initiation of the cultures, indicating that they may affect an early phase of lymphocyte activation. Compounds that induce erythroid differentiation in Friend leukemia cells constitute a new class of inhibitors of lymphocyte mitogenesis.