Effects of 6-aminonicotinamide on cell growth, poly(ADP-ribose) synthesis and nucleotide metabolism.
The purpose of this study was to determine if the cytotoxic effects of 6-aminonicotinamide are solely the result of an inhibition of poly(ADP-ribose) synthesis. The effects of 6-aminonicotinamide on cell growth, poly(ADP-ribose) synthesis and nucleotide concentrations were compared with the effect of 3-aminobenzamide, a more potent inhibitor of poly(ADP-ribose) synthesis. The growth of L1210 cells was not inhibited by 1 mM 3-aminobenzamide and was only slightly inhibited by 5 mM 3-aminobenzamide even though poly(ADP-ribose) synthesis, as measured by the N-methyl N-nitrosourea induced depletion of NAD+, was inhibited substantially. In contrast, 6-aminonicotinamide was found to be a potent inhibitor of L1210 and CHO cell growth. A 5 mM concentration of 3-aminobenzamide had no effect on purine and pyrimidine ribonucleotide concentrations or on the ATP to ADP ratio, but it did cause a slight elevation of NAD+. 6-Aminonicotinamide at 0.01 mM caused a depletion of purine and pyrimidine nucleotides and NAD+ as well as a reduction in the ATP to ADP ratio. 6-Aminonicotinamide at 1 mM caused a substantial inhibition of purine nucleotide synthesis from [14C] glycine but did not stimulate ATP breakdown. We conclude that inhibition of poly(ADP-ribose) synthesis caused little growth inhibition in itself and that the effects of 6-amininicotinamide on nucleotide metabolism were sufficient to produce an inhibition of both cell growth and DNA repair.
Hunting
D
D
Gowans
B
B
Henderson
J F
JF
D015120:6-Aminonicotinamide / Q000494:pharmacology*; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D006224:Cricetinae; D003412:Cricetulus; D004260:DNA Repair; D005260:Female; D009243:NAD / Q000378:metabolism; D009536:Niacinamide / Q000031:analogs & derivatives*; D009702:Nucleoside Diphosphate Sugars / Q000096:biosynthesis*; D009711:Nucleotides / Q000378:metabolism*; D011064:Poly Adenosine Diphosphate Ribose / Q000096:biosynthesis*
D009702:Nucleoside Diphosphate Sugars; D009711:Nucleotides; D009243:NAD; D009536:Niacinamide; D011064:Poly Adenosine Diphosphate Ribose; D015120:6-Aminonicotinamide; D000255:Adenosine Triphosphate