Influence of ADP-ribosyltransferase inhibitors on the intracellular NAD and ATP levels in Ehrlich ascites tumor cells: implication for the altered NAD + ATP-dependent cellular sensitivity to the cytotoxic agents.
Exposure of Ehrlich ascites tumor cells to 3-aminobenzamide for 60 min resulted in a dose-dependent increase of cellular NAD and ATP levels at a concentration range of 0.3-5 mM. In the cells exposed to 5-methylnicotinamide there was a decrease of both nucleotide levels. As a possible cause for these changes we found a marked inhibition of microsomal NAD glycohydrolase activity by 3-aminobenzamide and a moderate stimulation of this enzyme by 5-methylnicotinamide. Furthermore, 3-aminobenzamide significantly enhanced the cellular uptake of nicotinamide and NAD synthesis, probably by the stimulation of nuclear ATP-NMN adenylyltransferase activity. We show also that the cells containing elevated NAD and ATP levels by the exposure to 3-aminobenzamide became resistant to the 5-azacytidine cytotoxicity.
Robert Koch-Institute, Biochemistry Department, Berlin FRG.
J
J
Hoshino
S
S
Schalge
B
B
Drevenstedt
H
H
Kröger
D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D001374:Azacitidine / Q000494:pharmacology*; D001549:Benzamides / Q000494:pharmacology; D002286:Carcinoma, Ehrlich Tumor / Q000378:metabolism*; D005260:Female; D051379:Mice; D008861:Microsomes / Q000201:enzymology; D009243:NAD / Q000378:metabolism*; D009244:NAD+ Nucleosidase / Q000378:metabolism; D009536:Niacinamide / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology; D009612:Nicotinamide-Nucleotide Adenylyltransferase / Q000378:metabolism; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D014407:Tumor Cells, Cultured
D001549:Benzamides; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D009243:NAD; D009536:Niacinamide; C024785:5-methylnicotinamide; C025160:3-aminobenzamide; D000255:Adenosine Triphosphate; D009612:Nicotinamide-Nucleotide Adenylyltransferase; D009244:NAD+ Nucleosidase; D001374:Azacitidine; C024058:N(1)-methylnicotinamide