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 D...

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Bibliographic Details
Published in:British journal of cancer 2000-08, Vol.83 (4), p.514-518
Main Authors: Vaganay-Juéry, S, Muller, C, Marangoni, E, Abdulkarim, B, Deutsch, E, Lambin, P, Calsou, P, Eschwege, F, Salles, B, Joiner, M, Bourhis, J
Format: Article
Language:English
Subjects:
Amino Acid Sequence
Biological and medical sciences
Biomedical and Life Sciences
Biomedicine
Blotting, Western
Cancer Research
Cells
DNA Repair - physiology
DNA Repair - radiation effects
DNA-Activated Protein Kinase
DNA-Binding Proteins
Dose-Response Relationship, Radiation
Drug Resistance
Epidemiology
Humans
Kinases
Medical research
Medical sciences
Molecular Medicine
Molecular Sequence Data
Nuclear Proteins
Oncology
Protein-Serine-Threonine Kinases - metabolism
Protein-Serine-Threonine Kinases - radiation effects
Proteins
Radiation
Radiation therapy and radiosensitizing agent
Radiation Tolerance - physiology
Regular
regular-article
Treatment with physical agents
Treatment. General aspects
Tumor Cells, Cultured - enzymology
Tumor Cells, Cultured - radiation effects
Tumors
Yeast
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Summary: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. © 2000 Cancer Research Campaign
ISSN:0007-0920
1532-1827
DOI:10.1054/bjoc.2000.1258