DNA repair kinetics in mammalian cells following split-dose irradiation

The in situ DNA repair kinetics in intracerebral 9L tumor cells and cerebellar neurons following the second of two 1250- or 2500-rad doses separated by various times have been measured using alkaline sucrose gradients in zonal rotors. For both doses and all times employed, both cell types exhibited biphasic kinetics similar to those observed after single doses. When the two doses were separated by less than 2 hr in neurons (1 hr for tumor cells), the half-time (T1/2) of the slow phase was faster than that expected based on the amount of damage present and remained constant until the observed T1/2 coincided with the expected T1/2. When repair of the damage produced by the first dose was complete, the slow phase after the second dose exhibited the same T1/2 as after a single dose. These results suggest that the accessibility of a fraction of the chromatin is altered for a finite period during the repair process, and upon completion of repair is returned to a state indistinguishable from that existing prior to irradiation.