Response of human tumor cell lines in vitro to fractionated irradiation

The surviving fraction of human tumor cell lines after 2 Gy (SF2) varies between 0.1 and 0.8. It has been postulated that differences in inherent radiosensitivity of tumor cells are a major determinant of radiation response in vivo. Assays of inherent radiosensitivity based on acute survival are being developed as predictors of tumor response which often assume that the same inherent radiosensitivity persists throughout a fractionated treatment. We have investigated the response of 2 human tumor cell lines (A549 and MCF7) with different inherent radiosensitivities to in vitro fractionated irradiation. A549 cells had an SF2 of 0.62 and a mean inactivation dose (D) of 3.07 Gy whereas MCF7 cells had an SFZ of 0.30 and a D of 1.52 Gy. Split dose repair capacity (at equal survival levels) was less for A549 than for MCF7 cells and recovery kinetics for both cell lines were substantially longer than those of rodent cell lines. Survival after 5 fractions of 2 Gy given 12 hr apart at 37°C was near to that predicted from the acute survival curve, assuming complete repair and no proliferation. Acute survival of A549 cells which survived 5 fractions of 2 Gy given 12 hr apart was similar to the acute survival of unirradiated cells. When A549 cells were incubated at 22°C between 5 fractions of 2 Gy given 12 hr apart, proliferation and split dose repair were substantially inhibited. These studies support the proposals to use in vitro inherent radiosensitivity assays for the prediction of in vivo response of tumors to fractionated treatment.