Energy Parameters, Macromolecular Synthesis and Cell Cycle Progression of in vitro Grown Ehrlich Ascites Tumor Cells after Inhibition of Oxydative ATP Synthesis by Oligomycin

Abstract

In order to elucidate the significance of oxidative ATP production for the proliferation of Ehrlich ascites tumor cells, cell cycle progression, energy metabolism and macromolecular synthesis in the presence of oligomycin were studied. In the presence of the inhibitor (20 micrograms/ml), lactate production and glucose uptake of the cells increased by about 30-35% as compared to controls; oxygen consumption was maximally inhibited by 30-45% and could not further be reduced by higher concentrations of the inhibitor. ATP/ADP ratios of the oligomycin treated cells and control cells were not significantly different. In the first passage in the presence of oligomycin proliferation of the cells is reduced to about 50% that of controls; without severely affecting viability (dye exclusion test). In the second passage with oligomycin cell proliferation completely arrests. As was shown by flow cytometric analysis and BrdU-H33258 technique of flow cytometry, cells accumulate in the early S phase; division of cells which are in the S- and G2M compartment at the beginning of oligomycin treatment accounts for the increase of cell number in the first passage in the presence of oligomycin. On recultivation in the third passage in the absence of the inhibitor cells take up proliferation again; an increase of cell number of about 60% of controls was observed within 24 h. In the presence of oligomycin incorporation of [2-14C]thymidine is reduced to about 20% of the controls within 8 h, incorporation of [U-14C]lysine begins to slow down immediately after treatment with the inhibitor, the same is true for the incorporation of [2-14C]uridine.(ABSTRACT TRUNCATED AT 250 WORDS)