CELL-CYCLE CONSTRAINTS ON PEROXIDE-INDUCED AND RADIATION-INDUCED INHIBITORY CHECKPOINTS

The growth of human skin fibroblasts was reduced in a dose-dependent m anner after either treatment with hydrogen peroxide or exposure to ion izing radiation. Serum-starved cells were markedly responsive to the i nhibitory properties of large doses of either agent at any time during the first 12-14 h after restimulation. In contrast, when logarithmica lly growing cells were treated with hydrogen peroxide, a large percent age of G(1) cells synchronously traversed S phase in a wave that appea red after a 3-4 h delay, with a population of these cells eventually a rresting in tate S and G(2). An analogous compartment of cells exiting G(1) was not obvious when logarithmically growing cells were treated with ionizing radiation alone. However, when irradiated cells were sub sequently treated for 4 h with aphidicolin to depress ongoing DNA synt hesis to the levels seen in cultures treated with peroxide, a similar pattern of cells synchronously exiting G, was seen. Therefore, althoug h cells between G(0) and S had a marked sensitivity to the inhibitory effects of either peroxide or radiation, logarithmically growing cells in G(1) between hi and S were far less susceptible to either type of growth inhibition.