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 documented in the past few years. The molecular basis of this phenomenon remains largely unknown and the purpose of this study was to investigate the possible implication of the DNA repair DNA-PK complex. The activity of the DNA-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 decrease in DNA-PK activity was found in all six cell lines exhibiting HRS, whereas 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 occurring within the 2 h following low-dose radiation exposure. These data strongly suggest the implication of the DNA-PK repair complex in the HRS phenomenon.
Vaganay-Juéry
S
S
Unité Propre de l'Enseignement Supérieur 'Radiosensibilité humaine', UPRES, Villejuif, France.
Muller
C
C
Marangoni
E
E
Abdulkarim
B
B
Deutsch
E
E
Lambin
P
P
Calsou
P
P
Eschwege
F
F
Salles
B
B
Joiner
M
M
Bourhis
J
J
D000595:Amino Acid Sequence; D015153:Blotting, Western; D004260:DNA Repair / Q000502:physiology / Q000528:radiation effects; D051747:DNA-Activated Protein Kinase; D004268:DNA-Binding Proteins; D004307:Dose-Response Relationship, Radiation; D006801:Humans; D008969:Molecular Sequence Data; D009687:Nuclear Proteins; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism* / Q000528:radiation effects; D011836:Radiation Tolerance / Q000502:physiology*; D014407:Tumor Cells, Cultured / Q000201:enzymology / Q000528:radiation effects*
D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D051747:DNA-Activated Protein Kinase; C497263:PRKDC protein, human; D017346:Protein Serine-Threonine Kinases