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
Hoshino, J.; Schalge, S.; Drevenstedt, B.; Kröger, H.
Biochemistry International 20(1): 135-145
1990
ISSN/ISBN: 0158-5231 PMID: 1691642 Document Number: 364163
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 adenyryltransferase 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.