Carcinogenesis Advance Access originally published online on July 6, 2005
Carcinogenesis 2006 27(1):117-122; doi:10.1093/carcin/bgi175
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Carcinogenesis vol.27 no.1 © Oxford University Press 2005; all rights reserved.
The association of DNA-dependent protein kinase activity with chromosomal instability and risk of cancer
Department of Radiology, 1 First Department of Internal Medicine and 2 Department of Clinical Pathology, Sapporo Medical University, School of Medicine, Hokkaido, Japan, 3 Department of Radiation Research, Center for Disease Biology and Integrative Medicine, Graduate School of Medicine, University of Tokyo, Tokyo, Japan, 4 Department of Radiation Biosciences, Faculty of Pharmaceutical Sciences, Tokyo University of Science, Chiba, Japan and 5 Heavy-Ion Radiobiology Research Group, National Institute of Radiological Sciences, Chiba, Japan
* To whom correspondence should be addressed. Tel: +81 11 611 2111 (Ext. 3535); Fax: +81 11 613 9920; Email: sakatako{at}sapmed.ac.jp
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. In this study, 93 of untreated cancer patients and 41 of cancer-free healthy volunteers were enrolled. Peripheral blood was collected, separated and centrifuged; DNA-PK activity was measured by DNA-pull-down assay. The expressions of DNA-PKcs, Ku70 and Ku86 were examined by RTPCR 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, whereas DNA-PK activity and the expression of Ku70, Ku86 and DNA-PKcs in RTPCR were interrelated. A similar tendency was seen in western blot assay but less clear than in RTPCR. 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 conclusion, 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.
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