A G(1)-phase delay after exposure to a 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 alpha particles (0.19 or 0.57 Gy) and approximately equitoxic doses of gamma 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 alpha-particle-induced G(1)-phase delay in human skin fibroblasts even at the lowest dose, 0.19 Gy. At equitoxic doses, more pronounced and persistent G(1)-phase delays and arrests were observed in gamma-irradiated cultures in that increased fractions of the G(1)-phase cells remained BrdUrd(-) over the course of the study after gamma-ray exposure compared to cells exposed to alpha particles. In addition, G(1)-phase cells that became BrdUrd(+) after gamma irradiation re-arrested in G(1) phase, whereas BrdUrd(+) G(1)-phase cells in alpha-particle-irradiated cultures continued cycling. In contrast, comparable percentages of cells were delayed in G(2) phase after either alpha-particle or gamma irradiation. Both gamma and alpha-particle irradiation caused increases in cellular p53 and p21(Cip1) shortly after the exposures, which suggests that the G(1)-phase delay that occurs in response to alpha-particle irradiation is dependent on p53 like the initial G(1)-phase delay induced by gamma rays. (C) 1996 by Radiation Research Society