Cell Cycle Delays Induced by Heavy Ion Irradiation of Synchronous Mammalian Cells

Cell cycle delays in V79 Chinese hamster cells induced by heavy ion exposure have been investigated using flow cytometry. Synchronous cell populations in G1, S and late-S G2/M phase were used, which were prepared by centrifugal elutriation. Cells were irradiated with particles from Z = 10 (neon) up to 96 (uranium) in the energy range from 2.4 to 17.4 MeV/u and the LET range from 415 to 16,225 keV/micron at the UNILAC at GSI, Darmstadt. For comparison, experiments with 250 kV X-rays were performed. For light particles like neon, cell cycle perturbations comparable with those after X-ray irradiation were found, and with increasing LET an increasing delay per particle traversal was observed. For the highest LET values extended delavy in G1, S and G2/M phase were detected immediately after irradiation. A large fraction of the cells remained in S or G2/M phase up to 48 h or longer after irradiation: they probably died in interphase. The prolongation of delays with increasing LET is in contrast with inactivation cross section measurements, where cross sections reach a plateau at LET values > 500 keV/micron. No significant cell age dependence of cycle delays was detected for the very high LET values. In addition to cell cycle delays, two effects related to the DNA content as determined by flow cytometry were found after irradiation with very high LET particles, that were attributed to cell fusion and drastic morphological changes of the cells. Estimations based on the dose deposited by a single particle hit in the cell nucleus and the actual number of hits show that the basic trend of the experimental results can be explained by the stochastic properties of particle radiation.