Factors Influencing the Repair of Potentially Lethal Radiation Damage in Growth-Inhibited Human Cells

The cells in growth-inhibited (stationary phase) cultures of Chang human liver cells (LICH) will repair potentially lethal radiation damage (PLD repair) if allowed to remain in the stationary phase of growth for several hours after irradiation. The halftime for PLD repair was 1-2 hr, and it was associated with a change in the slope of the survival curve. Repair was independent of whether the cells reached stationary growth by density-inhibition or medium exhaustion. It depended upon both cell to cell contact and some factor which developed in the medium of stationary phase cultures. PLD repair was greatly reduced by incubating stationary cultures in fresh medium during the repair interval, whereas a small amount of repair with similar kinetics could be induced in exponentially growing cells by postirradiation incubation with conditioned medium from density-inhibited cultures. Incubation of stationary or exponentially growing cells with conditioned medium impeded the progression of G₁ cells into S. The repair process occurs primarily in cells in the G₁ phase of the life cycle. On the basis of these results, it is hypothesized that cells in stationary phase cultures are held up in a particular metabolic state in G₁ which favors the efficient repair of potentially lethal lesions. Conditions which allow the cells to leave this state and progress into S favor fixation of damage and reduced survival.