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  • Title: 1-Methylnicotinamide stimulates cell growth and inhibits hemoglobin synthesis in differentiating murine erythroleukemia cells.
    Author: Kuykendall JR, Cox R, Kinder D.
    Journal: Toxicol In Vitro; 2007 Dec; 21(8):1656-62. PubMed ID: 17826027.
    Abstract:
    Exposure of murine erythroleukemia cells (MELCs) to nicotinamide (NA) or its synthetic analog N'-methylnicotinamide (N'-MN) reduces cell growth and induces terminal differentiation, marked by increased heme and globin accumulation. On the contrary, 1-methylnicotinamide (1-MN), the primary metabolite of excess NA, was found to stimulate cell growth and reduce spontaneous differentiation of cultured MELCs. Log phase MELCs exhibited up to 50% higher cell density above untreated cells when cultured for up to 96 h with 2.5 mM 1-MN. When combined with NA or several chemically-unrelated inducers of hemoglobin synthesis in cultured MELCs, 1-MN reduced the globin mRNA levels and heme accumulation by 40-80%. 1-MN was able to inhibit heme production if present during only the first 24-48 h after NA exposure. Pre-treatment with 1-MN could not confer resistance of cells to effects of NA, suggesting the inhibition is reversible. Commitment to differentiate in semisolid medium by the most potent inducer, 5mM N'-MN, was inhibited up to 95% by 2.5mM concentrations of 1-MN. It appears that 1-MN has opposing effects on growth and induction of differentiation than those seen in MELC cultures exposed to NA or N'-MN.
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