Saturation of a DNA Repair Process in Dividing and Nondividing Mammalian Cells

Abstract

We have reported that the half-time (T1/2) for the slow phase of repair of radiation-induced DNA lesions increased with dose from 12.5 to 50.0 Gy in both 9L rat brain tumor cells and cerebellar neurons. In this manuscript these studies have been extended to lower doses to determine at what dose this DNA repair process becomes unsaturated. Our alkaline sucrose sedimentation technique in zonal rotors limits determination of the slow phase T1/2 to doses of greater than or equal to 6 Gy for 9L tumor cells and greater than or equal to 4 Gy for cerebellar neurons. The slow phase T1/2 in cerebellar neurons appears constant at doses less than or equal to 6 Gy and then increases exponentially at higher doses; survival of whole brain irradiated rats does not begin to decrease until doses greater than 6 Gy. The slow phase T1/2 in 9L tumor cells is either saturated or just becoming saturated at 6 Gy; a dose just before the final slope of the 9L survival curve is reached. These data support the hypothesis that the shape of mammalian cell survival curves is related to the saturation of a DNA repair process.