Characterization of the deoxynucleoside-dependent reversal of hypoxia-induced inhibition of cell cycle progression in Ehrlich ascites tumor cells.

Studies on Ehrlich ascites tumor cells enriched in different cell cycle compartments by centrifugal elutriation have shown that after exclusion of oxygen, G1- and early S-phase cells are restricted from further cell cycle progression. On addition of a balanced mixture of deoxypyrimidine and deoxypurine nucleosides to these anaerobic cultures (70% in G1-phase, as determined by flow cytometry), the cells resumed DNA synthesis and passed through the cycle. After 24 h, 19% of the cell population was still in G1. This cell cycle traverse does not seem to depend on RNA and protein synthesis. Using colcemid, mitotic activities became more evident in the presence of deoxynucleosides 20 h after establishing the protective atmosphere (argon/CO2). In the absence of colcemid binucleate cells could be detected. This was not observed in unsupplemented anaerobic cells. The ultrastructural changes of mitochondria in anaerobic cells resembled those in nucleoside-stimulated anaerobic cells: enlargement in profiles is accompanied by a simplification of cristae and a pallor of the intramatrical compartment. In addition, two different appearances of mitochondrial structures were visible if cells were cultured in the presence of deoxynucleosides.