Cell cycle constraints on peroxide- and radiation-induced inhibitory checkpoints.
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 G1 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 G2. An analogous compartment of cells exiting G1 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 G1 was seen. Therefore, although cells between G0 and S had a marked sensitivity to the inhibitory effects of either peroxide or radiation, logarithmically growing cells in G1 between M and S were far less susceptible to either type of growth inhibition.
Wharton
W
W
Life Sciences Division, Los Alamos National Laboratory, New Mexico 87545, USA.
D002453:Cell Cycle / Q000187:drug effects* / Q000528:radiation effects*; D002455:Cell Division / Q000187:drug effects / Q000528:radiation effects; D002478:Cells, Cultured; D004247:DNA / Q000096:biosynthesis / Q000187:drug effects / Q000528:radiation effects; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects* / Q000528:radiation effects*; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D016192:Resting Phase, Cell Cycle / Q000187:drug effects / Q000528:radiation effects; D012867:Skin / Q000166:cytology / Q000187:drug effects / Q000528:radiation effects
D004247:DNA; D006861:Hydrogen Peroxide