Oxygen-sensitive stages of the cell cycle of human diploid cells.

Abstract

Growth of human diploid WI-38 cells is reversibly inhibited by elevated partial pressures of oxygen (PO2 and interest was shown in determining where in the cell cycle growth was delayed [with respect to aging]. A technique combining cytospectrophotometry and autoradiography was used to determine cell cycle parameters. Confluent cells that were subcultivated and exposed to a PO2 of 365 .+-. 8 mm Hg were delayed primarily after DNA synthesis but before metaphase. At a PO2 of 590 .+-. 35 mm Hg, most cells did not initiate DNA synthesis, and the few that did, failed to complete the process. When exponentially growing cells that had already begun DNA synthesis were exposed to a PO2 of 590 .+-. 35 mm Hg, they accumulated after completing DNA synthesis but before initiating mitosis. The rate at which [3H]thymidine was incorporated into DNA was inversely correlated with O2 tension (PO2 of 135-590 mm Hg). Apparently the process most sensitive to O2 causes cells to be delayed after DNA synthesis but before metaphase. Slightly higher PO2 were needed to inhibit the initiation of DNA synthesis and the rate of DNA synthesis is decreased by elevated O2 tension.