Reduced DNA-dependent protein kinase activity is associated with lung cancer

Reduced DNA repair capacity of carcinogen-induced DNA damage is now thought to significantly influence inherent susceptibility to lung cancer. DNA-dependent protein kinase (DNA-PK) is a serine-threonine kinase activated by the presence of double-strand breaks in DNA that appears to play a major role...

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Bibliographic Details
Published in:Carcinogenesis (New York) 2001-05, Vol.22 (5), p.723-727
Main Authors: Auckley, Dennis H., Crowell, Richard E., Heaphy, Evelyn R., Stidley, Christine A., Lechner, John F., Gilliland, Frank D., Belinsky, Steven A.
Format: Article
Language:English
Subjects:
Adult
Aged
BECs
Biological and medical sciences
Bleomycin - pharmacology
bronchial epithelial cells
Case-Control Studies
Cell Survival - drug effects
DNA-Activated Protein Kinase
DNA-Binding Proteins
DNA-dependent protein kinase
DNA-PK
Female
Humans
Lung Neoplasms - enzymology
Lung Neoplasms - pathology
Male
Medical sciences
Middle Aged
New Mexico Veterans Health Care System
NMVHCS
Nuclear Proteins
odds ratio
peripheral mononuclear cells
PMs
Pneumology
Protein-Serine-Threonine Kinases - metabolism
Tumors of the respiratory system and mediastinum
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Summary:Reduced DNA repair capacity of carcinogen-induced DNA damage is now thought to significantly influence inherent susceptibility to lung cancer. DNA-dependent protein kinase (DNA-PK) is a serine-threonine kinase activated by the presence of double-strand breaks in DNA that appears to play a major role in non-homologous recombination and transcriptional control. The purpose of this study was to determine whether DNA-PK activity varies among individuals and how this affects lung cancer risk. DNA-PK activity in peripheral mononuclear cells from individuals with lung cancer (n = 41) was compared with lung cancer-free controls (n = 41). Interindividual variability was seen within each group, however, significant differences (P = 0.03) in DNA-PK activity between cases and controls were seen when comparing the distribution of enzyme activity among these two groups. The percentages of cases and controls with DNA-PK activity in the ranges 2.5–5.0 and 7.6–10.0 units were 39 versus 20% and 7 versus 29%, respectively. The enzyme activity in peripheral mononuclear cells reflected that seen in bronchial epithelial cells, one progenitor cell for lung cancer, supporting the use of peripheral mononuclear cells for larger population-based studies of DNA-PK activity. Its role as a potential modifier for lung cancer risk was supported by the fact that cell growth in bronchial epithelial cells exposed to bleomycin was directly associated with enzyme activity. The results of this study demonstrate that reduced DNA-PK repair activity is associated with risk for lung cancer.
ISSN:0143-3334
1460-2180
1460-2180
DOI:10.1093/carcin/22.5.723