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.
Someya
Masanori
M
Department of Radiology, Sapporo Medical University, School of Medicine, Hokkaido, Japan.
Sakata
Koh-ichi
K
Matsumoto
Yoshihisa
Y
Yamamoto
Hiroyuki
H
Monobe
Manami
M
Ikeda
Hideyuki
H
Ando
Koichi
K
Hosoi
Yoshio
Y
Suzuki
Norio
N
Hareyama
Masato
M
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