oa Peripheral Blood Lymphocyte Response To Γ-Radiation Exposure In Untreated Breast Cancer Patients

The level of double-strand DNA breaks (DSBs), DNA DSBs repair efficiency and apoptotic cell death frequency were analyzed in irradiated in vitro peripheral blood lymphocytes (γ-radiation of 60Co at dose of 1 Gy, dose-rate of 1 Gy/min) isolated from peripheral blood of 52 untreated breast cancer patients and 36 healthy donors using the DNA comet assay under nondenaturing conditions and the DNA halo assay, accordingly. The average DSB level in blood lymphocytes of breast cancer patients was shown to be significantly higher (p<0.05) compared with that in control donors. In general, the following effects were observed in irradiated in vitro lymphocytes of cancer patients: 1. increased sensitivity to γ-radiation, and 2. reduced efficiency of DNA DSBs repair. To estimate a possible impact of untargeted effects, the unirradiated cells were additionally incubated in a culture medium obtained from lymphocytes irradiated in vitro at doses of 1 Gy. Incubation of unirradiated blood lymphocytes in a medium from irradiated cells led to an increased relative number of DNA DSBs and an elevated fraction of cells dying through apoptotic pathway both in blood lymphocytes from cancer patients and control donors. However, these nontargeted effects were more pronounced for the blood lymphocytes of breast cancer patients. Summarizing the results of the study, we can conclude that the blood lymphocytes of breast cancer patients are characterized by a series of molecular and cellular features, detected by ionizing radiation exposure in vitro, in particular, increased yields of DNA DSBs, lower efficiency of DNA DSBs repair and more pronounced contribution of nontargeted effects of ionizing radiation.

A.N. Osipov, N.Yu. Vorobyeva, А.V. Аntonenko, V.V. Revin .