The cytokinetic basis for the design of efficacious radiotherapy protocols

Studies were performed to investigate the perturbing effects of ionizing radiations on the cell kinetics of T1699 transplantable mouse mammary tumors (MMT). Cell kinetic parameters included the 3H-TdR labeling index (LI), the DNA synthesis time (TS) and the primer dependent DNA polymerase labeling index (PDPI), an estimate of tumor growth fraction; they were determined by in vitro methods at various times after acute (400-1200 R) and fractionated (1000 R) X-irradiation. The cell kinetic response after both acute and fractionated treatment was generally similar and could be divided into four phases. (1) The initial phase of the response, occurring within the first 24 hr, was characterized by a decrease in 3H-TdR LI, an increase in PDPI and a concomitant lengthening of the TS. (2) The second phase was characterized by a variable, dose dependent interval of decreased cellular proliferation, as evidenced by a lengthening of TS and decreases in both PDPI and 3H-TdR LI. (3) The third phase of the response, the recovery phase, was characterized by increased cellular proliferation as evidenced by the recovery of TS to normal and increases in both PDPI and ³H-TdR LI to above control levels, in most cases. (4) The fourth phase of the response was characterized by a reestablishment of normal proliferative patterns. Studies with continuing radiotherapy schedules showed that the most effective schedules for local control and ILS were those in which radiation fractions were given just prior to initiation of observed proliferative recovery. The least effective schedules were those in which radiation fractions coincided with the time of maximal proliferative activity.