Oxygen dependent regulation of DNA synthesis and growth of Ehrlich ascites tumor cells in vitro and in vivo

Ehrlich ascites cells were cultured under different O2 partial pressures from less than 0.1 ppm to 2 x 10(5) ppm. During the artificial hypoxia and following reoxygenation the DNA synthesis rate was measured and the relative frequency of replicon initiations was examined by analyzing the length distributions of replicative daughter strand DNA. These studies were complemented by evaluation of growth and cycling of the cells and by biochemical analyses. It was demonstrated that the reversible shut-down of clusters of replication units already described before (Probst, H., Gekeler, V., and Helftenbein, E. Exp. Cell Res., 154: 327-341, 1984) occurred between 0.25 and about 2.5 microM dissolved O2. Above 2.5 microM, a transition range to aerobiosis extended to about 16 microM O2. Below 0.25 microM O2, the cells suffered damage impairing the reversibility of the shutdown. The observed changes of growth and cycling correlated well with the respective changes of replication. Analogous oxygenation dependent regulatory events in replication were also observed during growth of the cells as an in vivo ascites tumor. Obviously, the particular oxygenation conditions in the peritoneal cavity strongly influence tumor growth via the oxygen dependent regulation of replication.