A benchmark of cell survival models using survival curves for human cells after completion of repair of potentially lethal damage.

Six models of radiation action (the linear-quadratic model, the multitarget model with initial slope, the repair-misrepair model, the lethal-potentially lethal model, the cybernetic model, the saturable repair model) were tested for their goodness of fit to survival curves for human cells. Fifty-three survival curves for human cells irradiated in plateau phase and after completion of repair of potentially lethal damage (PLD) provided the experimental basis for the tests. Three criteria were considered. The capacity to describe the survival data was estimated, using the error left unexplained by the model. A validation of models was achieved by consideration of the mean residual squared errors. The ability of the parameters to characterize survival curves was investigated, studying their variation within and among curves. The models were not equivalent, whatever the test. The saturable repair model and the multitarget with initial slope model gave the most accurate description of survival data. The linear-quadratic model had the most reliable parameters, so that comparisons of the cell survival curves could be made advantageously. The cybernetic model and the lethal-potentially lethal model were found inappropriate for the analysis of survival curves for human cells after completion of PLD repair.

Dose-rate effects on the survival of irradiated hypersensitive and normal human fibroblasts.

The linear-quadratic model describes cell killing by radiation as due to two processes defined by the linear (alpha) component and by the quadratic (beta) component. As alpha and beta are interdependent, it is difficult to evaluate accurately the alpha component (which characterizes the intrinsic radiosensitivity). It has been suggested that irradiation at low dose-rate (around 1 cGy/min) allows the disappearance of the beta component and thus gives a direct measure of alpha. The present results verify this hypothesis with plateau phase cells. The survival of five human fibroblast cell lines in exponentially growing and density-inhibited, confluent cultures maintained at 37 degrees C following exposure to 60Co gamma-rays at dose-rates of 0.33-100 cGy/min followed by delayed plating (only for plateau phase cells) was monitored. Three of these cell lines are considered to be 'normal' and two are derived from hypersensitive individuals. The mean inactivation doses (D) of the five cell lines for acute doses with immediate plating were 173, 163, 136, 107 and 67 cGy. (D) increased with delayed plating recovery for 4 of the 5 cell lines and the survival of the 5 cell lines increased after low dose-rate exposure (1 cGy/min) without altering the ranking. The differences between cell lines (absolute values of (D) increased with decreasing the dose-rate. Analysis of the survival curves with the General Linear Quadratic (GLQ) model gave repair half-times for each cell line which were not correlated with the intrinsic radiosensitivities. Surprisingly, the alpha component decreased with decreasing dose-rate for all 5 cell lines (only in plateau phase). Thus low dose-rates do not allow direct measurement of the alpha component; the decrease in alpha could be interpreted as adaptive radioresistance.