Why are some human tumours more radiosensitive than others?

There is now good evidence that the radiosensitivity of human tumour cells varies form one tumour type to another, and that the steepness of the initial part of the cell survival curve correlates with clinical radioresponsiveness. Studies at low dose rate allow differences between tumour cells to be seen more clearly. Current mathematical models of radiation cell killing include two components: a linear (i.e. exponential "alpha-component") and a bending component ("beta-component"). Repair of radiation damage affects only the beta-component. Among the 17 human tumour cell lines that we have studied, the average surviving fraction at 2 Gy due to the alpha-component is 0.44 and that due to the beta-component is 0.88. The beta-effect at 2 Gy appears to be similar in radiosensitive and radioresistant tumours; thus among radiosensitive tumours where the survival due to the alpha-component is below 0.3 the beta-effect makes a very small contribution to overall radiosensitivity in the low-dose region. Steep cell survival curves may appear straight but still be consistent with a modest beta-value. The overall effect of many small fractions will be to amplify the dominance of the alpha-component. The beta-effect is then unimportant because repair will be almost complete. Repair inhibitors may however change this situation, reducing recovery, increasing the beta-effect, and thereby increasing sensitivity. But in the absence of such inhibitors the differences between radiosensitive and radioresistant tumours must be looked for not in repair capacity but in the nature of the alpha-component. The most radiocurable tumours do not have low beta-values; they have higher alpha-values than the less curable tumours.