DNA double-strand break (
DSB) is one of the most deleterious lesions induced by
DNA damaging agents.
DSB repair pathway is implicated in maintaining genomic integrity via suppression of genetic instability and neoplastic transformation.
DNA-dependent protein kinase (
DNA-PK) has a pivotal role in
DNA DSB repair. The
Nijmegen breakage syndrome protein (NBS1), essential for
DSB repair, re-localizes into subnuclear structures upon induction of DNA damage by ionizing radiation, forming so-called ionizing radiation-induced foci (IRIF), which is visualized by immunostaining. We measured
DNA-PK activity and the number of persistent NBS1 IRIF per nucleus 24 h after irradiation of peripheral blood lymphocytes (PBL) from patients with sporadic
breast cancer.
Chromosomal aberrations were examined by cytogenetic methods. We examined the relationship between these measurements and clinical characteristics of patients such as
tumor size,
lymph node metastasis and nuclear grade of
cancer cells. A higher number of NBS1 IRIF or lower
DNA-PK activity correlated with higher
chromosome instability. Patients whose PBL had lower
DNA-PK or higher NBS1 IRIF had aggressive
cancer phenotypes such as a larger
tumor, higher nuclear grade and positive axillary
lymph node metastasis. The combination of
DNA-PK activity and NBS1 IRIF were useful for predicting
lymph node metastasis. The ability of
DSB repair in PBL is related to aggressive
breast cancer phenotypes. Axillary
lymph node dissection can be avoided by examining
DNA-PK activity and NBS1 IRIF of PBL, which can contribute to improving the quality of life of
breast cancer patients.