Relationship between mitotic delay and the minimum dose rate of X irradiation required to stop cell proliferation

When cells are subjected to irradiation, their progression through the cell cycle can be arrested. If the arrested cells are subjected to additional damage, their period of arrest is prolonged. Under continuous low-dose-rate irradiation, the cumulative nature of arrest time leads to a geometric increase in the arrest time as a function of the dose rate. Above a certain cell-line-specific dose rate, the arrest duration becomes infinite and cell proliferation ceases. We find that the lowest dose rate (critical dose rate) required to stop cell proliferation during continuous irradiation is the reciprocal of the mitotic delay per gray of high-dose-rate irradiation. The calculated critical dose rates for X rays agree with those measured by Mitchell et al. (Radiat. Res. 79, 537-551, 1979), provided that the critical dose rate is identified with the minimum dose rate which allows no more than one population doubling. This specific identification of the critical dose rate is explained on the basis of cell cycle kinetics. A kinetic mechanism for cell cycle arrest and recovery leads to the critical dose rate as the reciprocal sensitivity for G2 arrest.