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 qu adratic (beta) component. As alpha and beta are interdependent, it is difficult to evaluate accurately the alpha component (which characteri zes the intrinsic radiosensitivity). It has been suggested that irradi ation at low dose-rate (around 1 cGy/min) allows the disappearance of the beta component and thus gives a direct measure of alpha. The prese nt results verify this hypothesis with plateau phase cells. The surviv al of five human fibroblast cell lines in exponentially growing and de nsity-inhibited, confluent cultures main tained at 37 degrees C follow ing exposure to Co-60 gamma-rays at dose rates of 0.33-100 cGy/min fol lowed by delayed plating (only for plateau phase cells) was monitored. Three of these cell lines are considered to be 'normal' and two are d erived from hypersensitive individuals. The mean inactivation doses (( D) over bar) of the five cell lines for acute doses with immediate pla ting were 173, 163, 136, 107 and 67 cGy. ((D) over bar) increased with delayed plating recovery for 4 of the 5 cell lines and the survival o f the 5 cell lines increased after low dose-rate exposure (1 cGy/min) without altering the ranking. The differences between cell lines (abso lute values of ((D) over bar) increased with decreasing the dose-rate. Analysis of the survival curves with the General Linear Quadratic (CL Q) model gave repair half-times for each cell line which were not corr elated with the intrinsic radiosensitivities. Surprisingly, the alpha component decreased with decreasing dose-rate for all 5 cell lines (on ly in plateau phase). Thus low dose-rates do not allow direct measurem ent of the alpha component; the decrease in alpha could be interpreted as adaptive radioresistance.