Survival based on colony formation was measured for starved plateau-phase Chinese hamster ovary (CHO) cells exposed to 250 kVp X rays at dose rates of 0.0031, 0.025, 0.18, 0.31, and 1.00 Gy/min. A large dose-rate effect was demonstrated. Delayed plating experiments and dose response experiments following a conditioning dose, both using a dose rate of 1.00 Gy/min and plating delays of up to 48 hr, were also used to investigate the alternative repair hypotheses. There is clearly a greater change in survival in dose-rate experiments than in the other experiments. Thus we believe that a process which depends on the square of the concentration of initial damage, and which alters the effect of initial damage on cell survival is being observed. We have applied the damage accumulation model to separate the single-event damage from this concentration-dependent form and estimate the repair rate for the latter type to be 70 min for our CHO cells. Use of this analysis on other published dose-rate studies also yields results consistent with this interpretation of the repair mechanisms.

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The interaction of biochemical processes and radiation damage appears to play a major role in determining long-term biological effects. It is responsible for both the removal of radiation-induced alterations in macromolecules and for the time-dependent changes in survival of irradiated cells. Restoration of macromolecules by such means as the rejoining of strand breaks in DNA suggests a variety of possible mechanisms which could lead to the observed enhancement of cell survival. However, even though a number of molecular repair mechanisms have been identified, specific links between any such mechanisms and a subsequent modification of cell survival have proved difficult, if not impossible, to demonstrate. Models of cellular response provide a means of attempting to establish this connection. Although details of radiation chemistry, chromatin structure, enzymatic repair, molecular genetics, and cell cycle kinetics are generally simplified, each individual model incorporates features based on a set of assumed mechanisms. For example, one group of models assumes that all damage is potentially lethal (capable of killing the cell unless it is repaired), while another assumes that part of the damage is sublethal (innocuous until it interacts with other damage). Using split-dose, dose-rate, and delayed-plating techniques, we have demonstrated two distinct components of repair in plateau-phase Chinese hamster ovary cells. One process has a characteristic time of about 1 h; the other, about 18 h. In both cases, the reaction rates and the fractions of damage repaired appear to be independent of the initial amounts of damage produced. These observations suggest that none of the simpler models adequately describes cell inactivation; i.e., reproductive death is inconsistent with all assumptions regarding any of them. Consequently, more-complex models involving combinations of sublethal and potentially lethal damage or multiple-step damage processes may be required. These findings help to define the effects of exposure at low doses and dose rates and to develop an understanding of the underlying biochemical mechanisms involved.