The ESTRO Breur lecture. Cellular sensitivity to low dose-rate irradiation focuses the problem of tumour radioresistance.

This paper emphasises the radiobiology of human tumour cells irradiated at the relatively low dose rate of 1 Gy/h (i.e.1-2 cGy/min), described here as the "Regaud dose rate". Continuous irradiation at this dose rate is approximately isoeffective with fractionated radiotherapy using 2 Gy/fractions. At the Regaud dose rate, cell survival curves are approximately exponential and they appear to extrapolate the initial slope of the high dose rate survival curve. Little recovery occurs after such treatments since it has largely taken place during irradiation. At the Regaud dose rate human tumour cell lines show a wide range of radiosensitivities, differing by a factor of around 7. This may well be the most clinically-relevant way of describing the radiosensitivity of tumour cells. Current models of radiation cell killing envisage a component of damage that increases linearly with dose. It is this component that dominates the slope of the Regaud survival curve. It may be produced by DNA damage due to clusters of ionisation events, or perhaps by damage to hypersensitive parts of the genome. The steepness of this component of damage may be modified by exogenous inhibitors of DNA damage repair.