Metabolic alterations in Yoshida ascites tumour cells caused by 6-aminonicotinamide and prevented by nicotinamide.

The CO-output in Yoshida ascites-tumour cells is markedly decreased, when washed ascites-tumour cells are incubated in vitro with [1-C]-glucose in the presence of 6-AN. Inhibition of CO-output increases with increasing concentrations of the drug. Similar results are obtained, when the drug (10, 25 or 50 mg/kg body weight) is administered intraperitoneally into mice bearing ascites-tumour and the ascites cells 9 h after treatment are incubated in vitro with [1-C]-glucose. Glucose-uptake in vitro is likewise lowered following treatment with 6-AN (50 mg/kg body weight). Measurements of metabolic intermediates in homogenates of such pretreated ascites-tumour cells reveal an immense accumulation of 6-phosphogluconate (70-fold) paralleled by a moderate increase in the content of glucose-6-phosphate (3-4-fold). The contents of glucose-1-phosphate and fructose-6-phosphate increase concomitantly. A 6-7-fold increase in the content of the triose phosphates (glyceraldehyde-3-phosphate and dihydroxyacetone phosphate) with a concomitant 5-6-fold increase in the content of fructose-1,6-diphosphate is also observed, whereas the contents of glycerol-1-phosphate, pyruvate, lactate, malate, and ATP are decreased; that of phosphoenolpyruvate is slightly raised. The ratio of glucose-6-phosphate to fructose-6-phosphate increases slightly from 3.5 for control assay systems to 4.2 following treatment with the drug. This is no significant increase and may suggest no inhibition of glycolysis by 6-phosphogluconate at the phosphoglucose isomerase level. The simultaneous intraperitoneal injection of nicotinamide (50 mg/kg body weight) abolishes or at least minimizes the metabolic effects caused by 6-AN. The data presented suggest inhibition of glycolysis and more effectively of the pentose phosphate pathway in ascites-tumour cells by in vivo synthesized NAD(P)-analogues of 6-AN. [ABSTRACT FROM AUTHOR]