Induction of gamma-H2AX Foci in Lymphocytes, Fibroblasts and Tumor Cells by Single and Pulsed High Dose Rate X-rays (original) (raw)
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Journal of Radiation Research
Phosphorylated H2AX (γH2AX) is a sensitive biomarker of DNA double-strand breaks (DSBs). To assess the adverse effects of low-dose radiation (<50 mGy), γH2AX levels have typically been measured in human lymphocytes within 30 min of computed tomography (CT) examinations. However, in the presence of DSB repair, it remains unclear whether γH2AX levels within 30 min of irradiation completely reflect biological effects. Therefore, we investigated the optimal timing of a γH2AX analysis to predict the cell-surviving fraction (SF). Three tumor cell lines were irradiated at different X-ray doses (10–4000 mGy), and the relationships between SF and relative γH2AX levels were investigated 15 min and 2, 6, 12 and 24 h after irradiation. Data were analyzed for high-dose (0–4000 mGy) and low-dose (0–500 mGy) ranges. Correlations were observed between SF and the relative number of γH2AX foci/nucleus at 12 h only (R2 = 0.68, P = 0.001 after high doses; R2 = 0.37, P = 0.016 after low doses). The r...
Radiation research, 2015
The biological risks associated with low-dose-rate (LDR) radiation exposures are not yet well defined. To assess the risk related to DNA damage, we compared the yields of two established biodosimetry end points, γ-H2AX and micronuclei (MNi), in peripheral mouse blood lymphocytes after prolonged in vivo exposure to LDR X rays (0.31 cGy/min) vs. acute high-dose-rate (HDR) exposure (1.03 Gy/min). C57BL/6 mice were total-body irradiated with 320 kVP X rays with doses of 0, 1.1, 2.2 and 4.45 Gy. Residual levels of total γ-H2AX fluorescence in lymphocytes isolated 24 h after the start of irradiation were assessed using indirect immunofluorescence methods. The terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay was used to determine apoptotic cell frequency in lymphocytes sampled at 24 h. Curve fitting analysis suggested that the dose response for γ-H2AX yields after acute exposures could be described by a linear dependence. In contrast, a linear-quadratic dose-respo...
Cancer research, 1992
The existence of heritable radiosensitivity syndromes and clinical observations in radiotherapy patients suggests that human cellular radiosensitivity differs among individuals. We report here an in vitro study of radiosensitivity in 30 fibroblast and 29 lymphocyte cultures obtained from cancer patients and controls. In 25 cases, both fibroblasts and lymphocytes were obtained from the same donors. Fibroblasts were cultured from skin biopsy samples, and peripheral T-cell lymphocytes were cultured from blood. Clonogenic survival assays were performed by using high- and low-dose-rate irradiation; lymphocytes were in G0 phase and fibroblasts in confluent plateau phase. Various end points were calculated and compared (i.e., surviving fraction at 2 Gy, initial slope of the survival curve, and doses resulting in 10 and 1% survival, respectively). Depending on the end point, the coefficient of variation of the survival parameters ranged from 31 to 68% for lymphocytes and 21 to 41% for fibro...