SYNERGISTIC ANTILEUKEMIC EFFECT OF 6-AMINONICOTINAMIDE AND 1,3-BIS(2-CHLOROETHYL)-1-NITROSOUREA ON L1210-CELLS INVITRO AND INVIVO

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  • 1 January 1982
    • journal article
    • research article
    • Vol. 42  (11) , 4382-4386
Abstract
A series of nicotinamide analogs were evaluated for their ability to inhibit L1210 cell poly(adenosine diphosphoribose) polymerase, and also for their ability to potentiate the cytocidal effects of 1,2-bis(2-chloroethyl)-1-nitrosourea (BCNU), nitrogen mustard, and .gamma.-irradiation in L1210 cells growing in culture and in vivo. In vitro, nicotinamide, 5-methylnicotinamide, 6-aminonicotinamide and benzamide effectively inhibited L1210 cell poly(adenosine diphosphoribose) polymerase; 1-methylnicotinamide, nicotinic acid and benzoic acid did not. In culture, 6-aminonicotinamide potentiated the cytocidal effect of BCNU; however, it did not significantly potentiate the effects of nitrogen mustard or .gamma.-irradiation. In vivo, both 6-aminonicotinamide and nicotinamide potentiated the cytocidal effect of BCNU; however, the concentrations of nicotinamide required for this effect were 10- to 20-fold higher than those of 6-aminonicotinamide. None of the analogs significantly potentiated the in vivo effect of nitrogen mustard or .gamma.-irradiation. Treatment of L1210-bearing mice with varying combinations of BCNU and 6-aminonicotinamide produced a synergistic increase in life span; in some cases, the combination led to the production of long-term disease-free survivors.