Differences in Replicon Behavior between X-Irradiation-Sensitive L5178Y Mouse Lymphoma Cells and A-T Fibroblasts Using DNA Fiber Autoradiography

Publisher Website
Google Scholar
Abstract
Replicon behavior in radiosensitive ataxia telangiectasia (A-T) [human] fibroblasts and mouse lymphoma L5178Y (LS) cells was studied by DNA fiber autoradiography. LS cells, irradiated at 13 Gy, showed a similar reduction in rate of DNA chain growth and initiation of replicons as did resistant (LR) cells. A progressive increase in the intensity of [3H]TdR [deoxythymidine] labeling of many replicons was observed after irradiation in the LS cells, but not in LR cells. This indicated a reduced or absent endogenous dTTP supply after irradiation in the LS cells, implicating a defect in nucleoside precursor production. Irradiated normal human and A-T cells did not show this effect. After 2 Gy, the frequency of initiation of replicons into synthesis was temporarily reduced in the normal human but not in the A-T cells. After 20 Gy, the rate of DNA chain growth was preferentially reduced in the normal human cells, but an increase was observed in the A-T cells. This increased rate could be explained in terms of a normal supply of complexes involved in chain elongation being distributed over a reduced number of initiated replicon clusters in the A-T cells.