Description:
Abstract The proliferation of in vitro grown Ehrlich ascites tumor cells is inhibited by pyruvate concentrations >2 mᴍ. In the presence of 4-5 mᴍ pyruvate the growth is reduced to about 50%, in the presence of 20 mᴍ to about 5 - 10%. Viability of the cells is not severely affected. Increase of DNA corresponds to the cell growth. On recultivation in pyruvate free standard medium, growth is nearly normal. Flow cytometric analyses of the proliferation kinetics of the cells in the presence of 20 mᴍ pyruvate revealed a retardation of the passage of all phases of the cell cycle. No phase specific effects could be detected though the S- and G2M-phase are more afflicted than Gl. The growth inhibition of EAT cells by pyruvate seems to depend on the presence of glucose. Exogenous pyruvate (>1-2 mᴍ) causes an activation of pyruvate dehydrogenase, a reduction of lactate production from glucose and a stimulation of lipid biosynthesis; the NAD/NADH ratio of the cells is reduced and a rise of glycolytic intermediates beyond glyceraldehyde-3-phosphate dehydrogenase is observed. Maximal activation of pyruvate dehydrogenase by non toxic concentrations of dichloroacetate is also accompagnied by an inhibition of cell growth. It is suggested that an increase of glyceraldehyde-3-phosphate level and the changes in the redox state of the cells are of relevance for the inhibition of cell growth by pyruvate. 100-500 μᴍ exogenous glycer-aldehyde-3-phosphate strongly inhibited cell growth.