Alterations in the Progression of Cells through the Cell Cycle after Exposure to Alpha Particles or Gamma Rays

A G₁-phase delay after exposure to α particles has not been reported previously, perhaps because immortalized cell lines or cell lines from tumor cells were used in past studies. Therefore, we compared the effects of α particles (0.19 or 0.57 Gy) and approximately equitoxic doses of γ rays (2 or 4 Gy) on progression of cells through the cell cycle in normal human skin fibroblasts. Cell cycle analyses were performed using flow cytometry by measuring incorporation of bromodeoxyuridine (BrdUrd) in each phase of the cell cycle up to 44 h after irradiation. We observed an α-particle-induced G₁-phase delay in human skin fibroblasts even at the lowest dose, 0.19 Gy. At equitoxic doses, more pronounced and persistent G₁-phase delays and arrests were observed in γ-irradiated cultures in that increased fractions of the G₁-phase cells remained${\rm BrdUrd}^{-}$ over the course of the study after γ-ray exposure compared to cells exposed to α particles. In addition, G₁-phase cells that became BrdUrd⁺ after γ irradiation re-arrested in G₁ phase, whereas BrdUrd⁺ G₁-phase cells in α-particle-irradiated cultures continued cycling. In contrast, comparable percentages of cells were delayed in G₂ phase after either α-particle or γ irradiation. Both γ and α-particle irradiation caused increases in cellular p53 and p21 ^Cip1 shortly after the exposures, which suggests that the G₁-phase delay that occurs in response to α-particle irradiation is dependent on p53 like the initial G₁-phase delay induced by γ rays.