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High and Low Fluences of -Particles Induce a G₁ Checkpoint in Human Diploid Fibroblasts¹

Department of Cancer Cell Biology, Laboratory of Radiobiology, Harvard School of Public Health, Boston, Massachusetts 02115 [E. I. A., S. M. d. T., J. B. L.], and Radiation Biology and Health Physics, Atomic Energy of Canada Ltd., Ontario K0J 1J0, Canada [A. J. W.]

The effects of exposure to high and very low fluence -particles on the G₁ checkpoint were investigated in human diploid fibroblasts irradiated and released from density-inhibited confluent cultures by the use of the cumulative labeling index method. Transient and permanent arrests in G₁ occurred in fibroblast populations exposed to mean doses as low as 1 cGy, suggesting that nontraversed bystander cells may contribute to the low dose response. In cells exposed to high fluences, the G₁ checkpoint is at least as extensive as in -irradiated cells. In contrast to -irradiated cells, neither repair of potentially lethal damage nor a reduction in the fraction of cells transiently or permanently arrested in G₁ were observed in cells held in confluence for 6 h after -particle irradiation. Studies with isogenic wild-type, p53^–/–, and p21^Waf1–/– mouse embryo fibroblasts exposed to either or -particle radiation revealed a total lack of G₁ arrest in either p53^–/– or p21^waf1–/– cells, indicating that the G₁ checkpoint in wild-type cells is p53-dependent and that p21^Waf1 fully mediates the role of p53 in its induction. In contrast to human cells, mouse embryo fibroblasts do not undergo a permanent G₁ arrest. Except under conditions favoring potentially lethal damage repair, a comparable expression pattern of p53, p21^Waf1, and other cell cycle-regulated proteins (pRb, p34^cdc2, and cyclin B₁) was observed in -particle or -irradiated human fibroblasts.

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