Induction of erythroid differentiation of murine erythroleukemia cells by nicotinamide and related compounds.

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Abstract
Nicotinamide and its analogues were evaluated for their activity as inducers of differentiation of murine erythroleukemia cells [DS19] in culture. N''-Methylnicotinamide was the most effective of the compounds tested; at its optimal concentration it was more effective than dimethyl sulfoxide. With 8-10 mM N''-methylnicotinamide, almost all the cells contained hemoglobin (benzidine-reactive) after a 60 h culture. Commitment to differentiate, assayed by transfer of the cells to semisolid medium without inducers, occurred much earlier and was more extensive with N''-methylnicotinamide than with dimethyl sulfoxide or nicotinamide. Increase in globin mRNA was greater in the cells cultured with N''-methylnicotinamide than in cells cultured with dimethyl sulfoxide or nicotinamide. The relationship between the inducing activities of nicotinamide analogues and their effect on poly(ADP-ribose) polymerase in vitro was studied. All the compounds studied that had strong inhibitory effects on poly(ADP-ribose) polymerase in vitro induced differentiation of erythroleukemia cells in culture. This property is not a prerequisite of inducers; N''-methylnicotinamide did not inhibit the enzyme in vitro.