A comparative study on proliferation, macromolecular synthesis and energy metabolism of in vitro-grown Ehrlich ascites tumor cells in the presence of glucosone, galactosone and methylglyoxal

Proliferation of in vitro grown Ehrlich ascites tumor cells is completely inhibited by 0.2-0.4 mM methylglyoxal and 1-2 mM glucosone or galactosone without severely affecting viability (dye exclusion test); no phase-specific arrest of cell growth is observed. Incorporation of [14C] thymidine into the acid-insoluble fraction of the cells decreases within a few minutes to less than 50% of that in controls in the presence of 0.4 mM methylglyoxal, and 2 mM glucosone or galactosone causes a comparable inhibition of DNA synthesis after 2 h or 4 h, respectively. The action of 0.4 mM methylglyoxal inhibits incorporation of [14C] leucine within a few minutes by more than 70%, while 2 mM glucosone and galactosone are significantly less effective (50%-60% inhibition after 12 h). While methylglyoxal and galactosone do not severely affect lactate production of the cells, 2 mM glucosone reduces glycolysis by 60%-70%; ATP/ADP ratios did not fall below 3.5 in the presence of the inhibitors (controls 4-6). It is suggested that the reaction potentialities of the oxaldehyde function of the inhibitors play an important role in their growth-inhibitory activity, besides exerting a specific effect on Hexokinase (glucosone) and UTP-trapping activity.