Cell cycle constraints on peroxide- and radiation-induced inhibitory checkpoints
Wharton, W.
Cancer Research 55(21): 5069-5074
1995
ISSN/ISBN: 0008-5472 PMID: 7585553 Document Number: 450391
The growth of human skin fibroblasts was reduced in a dose-dependent manner after either treatment with hydrogen peroxide or exposure to ionizing radiation. Serum-starved cells were markedly responsive to the inhibitory properties of large doses of either agent at any time during the first 12-14 h after restimulation. In contrast, when logarithmically growing cells were treated with hydrogen peroxide, a large percentage of G-1 cells synchronously traversed S phase in a wave that appeared after a 3-4 h delay, with a population of these cells eventually arresting in late 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 subsequently treated for 4 h with aphidicolin to depress ongoing DNA synthesis to the levels seen in cultures treated with peroxide, a similar pattern of cells synchronously exiting G-1 was seen. Therefore, although 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 M and S were far less susceptible to either type of growth inhibition.