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

Abstract

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.

Cell cycle arrest and aberration yield in normal human fibroblasts. I. Effects of X‐rays and 195 MeV u−1C ions

“…Particle exposure induces pronounced cell cycle delays (e.g. Scholz et al 1994, Ritter et al 1996, and these delays are related to the aberration burden of cells. For normal human fibroblasts, which respond to DNA damage not only with a transient, but also with a long-term cell cycle arrest (figure 2 and 3) (see Sections 4.1.1 and 4.1.2), the relationship between cell cycle effects and the expression of aberrations in metaphase cells might be even more complex.…”

Cell cycle arrest and aberration yield in normal human fibroblasts. II: Effects of 11 MeV u−1C ions and 9.9 MeV u−1Ni ions

“…Yet, evidence is growing that this assay is not reliable in the case of high LET radiation. The exposure of cells to high linear energy transfer (LET) radiation delays cell cycle progression more than exposure to low LET radiation (e.g., Collyn-D'Hooghe et al 1981, Lü cke-Huhle et al 1982, Scholz et al 1994) and it has been recently shown that the delay is related to the number of aberrations harboured by a cell. For example, in human lymphocyte populations exposed to particles with an LET exceeding 100 keV mm 71 , a signficant increase in the aberration yield with sampling time was observed.…”

Bestrahlung von Schädelbasistumoren mit Kohlenstoffionen bei der GSI Erste klinische Ergebnisse und zukünftige Perspektiven

“…Zellzyklusbedingte Unterschiede in der Radiosensitivität von Zellen sind gering, so dass sich Unterschiede in der Therapieantwort langsam und schnell proliferierender Tumoren reduzieren sollten. Es wurden zudem eine Verzögerung der Zellteilung nach Hoch-LET-Bestrahlung sowie eine Abnahme der Schutzeffekte durch die benachbarten Zellen beschrieben [2,17].…”