Chemical inhibition of recovery from radiation damage in mammalian cells

The impairment of the cell ability to recover from radiation damage would be of great interest in cancer treatments. Many chemicals are known to enhance the inactivation effect of ionizing radiation on various cellular systems. The enhancement may be due to both direct chemical toxicity and to the increase in the cellular sensitivity to radiation. The inhibition of cell recovery may proceed via either the damage of the mechanism of the recovery itself or via the formation of irreversible damage which could not be repaired at all. Both of the processes may take place at the same time. Any of these possibilities would result in a decrease in both the rate and extent of cell recovery. To distinguish them, a quantitative approach which describes the process of recovery as a decrease in the effective radiation dose was applied to experimental data on the recovery from potentially lethal damage in mammalian cells exposed to X-rays alone or combined with various chemicals. The survival increase due to recovery observed in the control cells gradually reduced as the chemical concentration increased, which meant that the inhibition of the recovery was drug concentration dependent. The obvious increase in the irreversible component with drug concentration should certainly lead to a decrease in the recovery rate because of the decrease in the number of cells capable of recovery. Taken together, it could be concluded that the recovery process itself was not affected and that the inhibition of the recovery is entirely due to the enhanced yield of the irreversibly damaged cells. The results of the present study provide opportunity for searching agents, selectively or simultaneously acting on the probability of recovery and the yield of irreversible radiation damage. (author)