RADIATION-INDUCED DNA-DAMAGE AND REPAIR IN CELLS OF A RADIOSENSITIVE HUMAN-MALIGNANT GLIOMA CELL-LINE

The induction and repair of DNA double-strand breaks were studied in c ells of two isogenic human malignant glioma cell lines which vary in t heir SF2 values by a factor of similar to 30. M059J cells are radiosen sitive (SF2 = 0.02) and lack the p350 component of DNA-dependent prote in kinase (DNA-PK); M059K cells are radioresistant (SF2 = 0.64) and ex press normal levels of DNA-PK. Zero integrated field gel electrophores is and alkaline sucrose gradient experiments indicated that equivalent numbers of DNA lesions were produced by ionizing radiation in M059J a nd M059K cells. To compare the capacity of both lines to repair sublet hal damage, the split-dose recovery experiment after exposure to equit oxic doses of radiation was carried out. Significant sublethal damage repair was shown for M059K cells, with a 5.8-fold increase in relative survival peaking at 4 h, whereas M059J cells showed little repair act ivity. Electrophoresis studies indicated that more double-strand break s were repaired by 30 min in M059K cells than in M059J cells. These re sults suggest that deficient DNA repair processes may be a major deter minant of radiosensitivity in M059J cells. (C) 1995 by Radiation Resea rch Society