Carcinogenesis Advance Access published online on July 6, 2005
Carcinogenesis, doi:10.1093/carcin/bgi175
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1 Department of Radiology, Sapporo Medical University, School of Medicine, Hokkaido, Japan
* To whom correspondence should be addressed. The DNA double strand breaks (DSBs) repair pathway has been implicated in maintaining genomic integrity via suppression of chromosomal rearrangements. DNA-dependent protein kinase (DNA-PK) has an important role with DNA DSBs repair. Ninety three of untreated cancer patients and forty one of cancer-free healthy volunteers were entered in this study. Peripheral blood was collected, separated, centrifuged. DNA-PK activity was measured by DNA-pull-down assay. The expressions of DNA-PKcs, Ku70, and Ku86 were examined by RT-PCR assay and Western blotting. Chromosomal aberrations were examined by cytogenetic methods. DNA-PK activities of peripheral blood lymphocytes (PBL) in patients with uterine cervix or breast cancer were significantly lower than those in normal volunteers. Age and smoking had no association with DNA-PK activity. There was the relationship between DNA-PK activity and expression of Ku70, Ku86, and DNA-PKcs in RT-PCR. The similar tendency in Western blot assay was seen but less clearer than RT-PCR. Therefore, the association between DNA-PK activity and expression of DNA-PK in protein level could not be concluded. The frequency of chromosome aberration such as dicentric chromosomes and excess fragment increased as the DNA-PK activity decreased. In conclusions, DNA-PK activity is associated with chromosomal instability. DNA-PK activity in PBL is associated with risk of breast and uterine cervix cancer. DNA-PK activity in PBL can be used to select individuals for whom an examination should be performed because of their increased susceptibility to breast and uterine cervix cancer.
Received April 26, 2005
Revised June 5, 2005
Accepted June 28, 2005
MOLECULAR EPIDEMIOLOGY AND CANCER PREVENTION
The association of DNA-dependent protein kinase activity with chromosomal instability and risk of cancer
2 Department of Radiation Research Center for Disease Biology and Integrative Medicine, Graduate school of Medicine, University of Tokyo, Tokyo, Japan
3 First Department of Internal Medicine, Sapporo Medical University, School of Medicine, Hokkaido, Japan
4 Department of Radiation Biosciences, Faculty of Pharmaceutical Sciences, Tokyo University of Science, Chiba, Japan
5 Department of Clinical Pathology, Sapporo Medical University, School of Medicine, Hokkaido, Japan
6 Heavy-Ion Radiobiology Research Group, National Institute of Radiological Sciences, Chiba, Japan
Koh-ichi Sakata, E-mail: sakatako{at}sapmed.ac.jp
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