The association of DNA-dependent protein kinase activity with chromosomal instability and risk of cancer.
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 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, whereas DNA-PK activity and the expression of Ku70, Ku86 and DNA-PKcs in RT-PCR were interrelated. A similar tendency was seen in western blot assay but less clear than in 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 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.
Department of Radiology, Sapporo Medical University, School of Medicine, Hokkaido, Japan.
Masanori
M
Someya
Koh-ichi
K
Sakata
Yoshihisa
Y
Matsumoto
Hiroyuki
H
Yamamoto
Manami
M
Monobe
Hideyuki
H
Ikeda
Koichi
K
Ando
Yoshio
Y
Hosoi
Norio
N
Suzuki
Masato
M
Hareyama
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D034961:Antigens, Nuclear / Q000235:genetics / Q000378:metabolism; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000097:blood / Q000201:enzymology / Q000235:genetics; D016022:Case-Control Studies; D043171:Chromosomal Instability; D002869:Chromosome Aberrations; D020732:Cytogenetic Analysis; D004260:DNA Repair; D051747:DNA-Activated Protein Kinase / Q000235:genetics* / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D004938:Esophageal Neoplasms / Q000097:blood / Q000201:enzymology / Q000235:genetics; D005260:Female; D006258:Head and Neck Neoplasms / Q000097:blood / Q000201:enzymology / Q000235:genetics; D006801:Humans; D000072200:Ku Autoantigen; D008223:Lymphoma / Q000097:blood / Q000201:enzymology / Q000235:genetics; D008297:Male; D008875:Middle Aged; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012307:Risk Factors; D012907:Smoking; D002583:Uterine Cervical Neoplasms / Q000097:blood / Q000201:enzymology / Q000235:genetics
D034961:Antigens, Nuclear; D004268:DNA-Binding Proteins; D051747:DNA-Activated Protein Kinase; C000606509:Xrcc6 protein, human; D000072200:Ku Autoantigen