Open AccessInduction of erythroid differentiation of murine erythroleukemia cells by nicotinamide and related compounds.
Author(s) -
Masaaki Terada,
Hirota Fujiki,
Paul A. Marks,
Takashi Sügimura
Publication year - 1979
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.76.12.6411
Subject(s) - nicotinamide , dimethyl sulfoxide , in vitro , biochemistry , inducer , benzidine , chemistry , cellular differentiation , microbiology and biotechnology , cell culture , enzyme , polymerase , biology , gene , genetics , organic chemistry
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.