Delayed reproductive death in X-irradiated Chinese hamster ovary cells

The cytotoxic effects of X-irradiation may be delayed for many generations of replication in mammalian cells. In addition to a reduced cloning efficiency, progeny of surviving Chinese hamster ovary (CHO) cells isolated after 12-34 population doublings postirradiation showed a variety of abnormalities including lower attachment ability to culture dishes and slower cell cycle progression. When these progeny were seeded as single cells 12-23 generations after irradiation, they formed a higher fraction of abortive colonies and of non-homogeneous colonies containing giant cells. All of these characteristics were evident whether progeny cells were subcultured by trypsinization or by mitotic selection. These results suggest that residual damage may be carried by surviving progeny of irradiated cells over many mitotic cycles; this damage is eventually expressed in terms of pleomorphic changes leading to delayed reproductive failure.