The dose-rate effect in human tumour cells.

The radiation response of 12 cell lines derived from a variety of human tumours has been investigated over the dose-rate range from 150 to 1.6 cGy/min. As the dose rate was lowered, the amount of sparing varied widely; in 2 cell lines it was zero, in the other cell lines the dose required for 10(-2) survival ranged up to twice the value at high dose rate. Low dose-rate irradiation discriminates better than high dose rate between tumour cell lines of differing radiosensitivity. The data are equally well fitted by two mathematical models of the dose-rate effect: the LPL model of Curtis and the Incomplete Repair model of Thames. Analysis by the LPL model leads to the conclusion that the theoretical radiosensitivity in the total absence of repair was rather similar among the 7 cell lines on which this analysis was possible. What differs among these cell lines is the extent of repair and/or the probability of direct infliction of a non-repairable lesion. Recovery from radiation damage was also examined by split-dose experiments in a total of 17 human tumour cell lines. Half-time values ranged from 0.36 to 2.3 h and there was a systematic tendency for split-dose halving times to be longer than those derived from analysis of the dose-rate effect. This could imply that cellular recovery is a two-component process, low dose-rate sparing being dominated by the faster component. The extent of low dose-rate sparing shows some tendency to correlate with the magnitude of split-dose recovery; in our view the former is the more reliable measure of cellular recovery. The clinical implication of these studies is that some human tumour types may be well treated by hyperfractionation or low dose-rate irradiation, while for others these may be poor therapeutic strategies.