Association of ionizing radiation-induced foci of NBS1 with chromosomal instability and breast cancer susceptibility.
NBS1, a protein essential for DNA double-strand break repair, relocalizes into subnuclear structures upon induction of DNA damage by ionizing radiation, forming ionizing radiation-induced foci. We compared radiation-induced NBS1 foci in peripheral blood lymphocytes (PBLs) from 46 sporadic breast cancer patients and 30 healthy cancer-free volunteers. The number of persistent radiation-induced NBS1 foci per nucleus at 24 h after irradiation for patients with invasive cancer was significantly higher than for normal healthy volunteers. The frequency of spontaneous chromosome aberration increased as the number of persistent radiation-induced NBS1 foci increased, indicating that the number of persistent radiation-induced NBS1 foci might be associated with chromosome instability. There was also an inverse correlation between the number of radiation-induced NBS1 foci and the activity of DNA-dependent protein kinase (DNA-PK), which plays an important role in the nonhomologous end-joining (NHEJ) pathway, another mechanism of DNA DSB repair, indicating a close interrelationship between homologous recombination (HR) and NHEJ in DNA DSB repair. In conclusion, the number of persistent radiation-induced NBS1 foci is associated with chromosomal instability and risk of sporadic breast cancer and hence might be used to select individuals for whom a detailed examination is necessary because of their increased susceptibility to breast cancer, although refinement of the techniques for technical simplicity and accuracy will be required for clinical use.
Someya
Masanori
M
Department of Radiology, Sapporo Medical University, School of Medicine, Hokkaido, Japan.
Sakata
Koh-ichi
K
Tauchi
Hiroshi
H
Matsumoto
Yoshihisa
Y
Nakamura
Asako
A
Komatsu
Kenshi
K
Hareyama
Masato
M
D001943:Breast Neoplasms / Q000209:etiology / Q000235:genetics*; D018797:Cell Cycle Proteins / Q000235:genetics* / Q000528:radiation effects*; D043171:Chromosomal Instability / Q000235:genetics* / Q000528:radiation effects*; D004307:Dose-Response Relationship, Radiation; D020022:Genetic Predisposition to Disease / Q000209:etiology / Q000235:genetics; D006801:Humans; D008214:Lymphocytes / Q000528:radiation effects*; D009687:Nuclear Proteins / Q000235:genetics* / Q000528:radiation effects*; D011829:Radiation Dosage; D011839:Radiation, Ionizing; D014407:Tumor Cells, Cultured
D018797:Cell Cycle Proteins; C112156:NBN protein, human; D009687:Nuclear Proteins