Induction of differentiation of the human histiocytic lymphoma cell line U-937 by retinoic acid and cyclic adenosine 3':5'-monophosphate-inducing agents.

The monoblast-like human histiocytic lymphoma cell line, U-937, is induced to differentiate into monocyte-like cells by incubation with 0.1 to 1.0 microM retinoic acid (RA). These induced cells are phagocytic, reduce nitroblue tetrazolium, and show an increased hexose monophosphate shunt activity, consistent with monocyte-like cells. Prostaglandin E, cholera toxin, or dibutyryl cyclic adenosine 3':5'-monophosphate, all inactive alone, increased markedly the extent of RA-induced differentiation of U-937. These data suggest that the intracellular level of cyclic adenosine 3':5'-monophosphate is of importance for expression of the RA-induced effect. Responsiveness to RA seems to be limited to those leukemic myeloid cells blocked at a relatively late stage of maturation, like the promyelocytic HL-60 and the monoblast-like U-937 cell lines.