Decreased DNA-PK activity in human cancer cells exhibiting hypersensitivity to low dose irradiation

Low-dose hyper-radiosensitivity (HRS) (below 0.5 Gy) has been extensively d ocumented in the past few years. The molecular basis of this phenomenon rem ains largely unknown and the purpose of this study was to investigate the p ossible implication of the DNA repair DNA-PK complex. The activity of the D NA-PK complex, i.e, Ku DNA-end binding activity and kinase activity of the whole complex, was studied in 10 human cancer cell lines, 2 h after 0.2, 0. 5 and 1 Gy irradiation. After low-dose irradiation (0.2 Gy), a marked decre ase in DNA-PK activity was found in all six cell lines exhibiting HRS, wher eas the DNA-PK activity was increased in the four cell lines which did not exhibit HRS. This modulation of DNA-PK activity was a rapid phenomenon occu rring within the 2 h following low-dose radiation exposure. These data stro ngly suggest the implication of the DNA-PK repair complex in the HRS phenom enon. (C) 2000 Cancer Research Campaign.