Relative contributions of levels of initial DNA damage and repair of double strand breaks to the ionizing radiation-sensitive phenotype of the Chinese hamster cell mutant, XR-V15B. Part I. X-rays.

In order to investigate the relationships between the induction and rejoining of DNA double-strand breaks (dsb) and their biological consequences it is necessary to measure these lesions uniquely and accurately, especially at relevant low doses of ionizing radiation. Differences in radiosensitivity between cell lines could be due to variations in dsb induction or to differences in the efficiency and/or accuracy of enzymatic repair of these lesions. We have used field-inversion gel electrophoresis to investigate dsb induction and rejoining in V79B parental and XR-V15B ionizing radiation-sensitive mutant cell lines. No difference has been found in the induction of dsb in XR-V15B cells compared with wild type cells; the assay sensitivity permits measurement of dsb induced by doses as low as 1 Gy (p < or = 0.05). The radiosensitivity of the mutant cells is manifested both in a lower fraction of dsb rejoined in the early, fast repair component and longer persistence of unrejoined dsb during post-irradiation incubation. The fraction of dsb remaining unrejoined after prolonged incubations (up to 17 h) correlates well with the higher radiosensitivity of the mutant (as judged by D10 values).