title: Induction of erythroid differentiation of murine erythroleukemia cells by nicotinamide and related compounds.
abstract: Nicotinamide and its analogues were evaluated for their activity as inducers of differentiation of murine erythroleukemia cells 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-hr 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 that 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.
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D004920:Erythropoiesis / Q000187:drug effects*; D005622:Friend murine leukemia virus; D005914:Globins / Q000096:biosynthesis; D004915:Leukemia, Erythroblastic, Acute / Q000473:pathology*; D007942:Leukemia, Experimental / Q000473:pathology; D051379:Mice; D009243:NAD / Q000378:metabolism; D009536:Niacinamide / Q000031:analogs & derivatives / Q000494:pharmacology*; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism
chemical_list: D012333:RNA, Messenger; D009243:NAD; D009536:Niacinamide; D005914:Globins; D011065:Poly(ADP-ribose) Polymerases