Dose rate effect on micronucleis induction in cytokinesis blocked human peripheral blood lymphocytes

Bhat, NN; Bs, Rao

doi:10.1093/oxfordjournals.rpd.a006333

Cited by 18 publications

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“…Radiation-induced chromosomal aberrations observed as MNi in peripheral blood lymphocytes are largely the result of unrepaired or misrepaired DSBs by the non-homologous end-joining pathway (36, 38). The dose-response relationship for micronuclei frequencies in human (39, 40) and mouse (41) peripheral blood lymphocytes (PBLs) in vitro after acute doses of ionizing radiation can be fitted with the linear-quadratic model. Studies aimed to investigate dose-rate effects for radiation-induced micronucleus formation in human lymphocytes reported that MNi yields decreased with decreasing dose rates (39, 42, 43).…”

Section: Introductionmentioning

confidence: 99%

Effect of Dose Rate on Residual γ-H2AX Levels and Frequency of Micronuclei in X-Irradiated Mouse Lymphocytes

et al. 2015

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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-response shape was more appropriate for LDR exposure (perhaps reflecting differences in repair time after different LDR doses). Dose-rate sparing effects (P < 0.05) were observed at doses ≤2.2 Gy, such that the acute dose γ-H2AX and TUNEL-positive cell yields were significantly larger than the equivalent LDR yields. At the 4.45 Gy dose there was no difference in γ-H2AX expression between the two dose rates, whereas there was a two- to threefold increase in apoptosis in the LDR samples compared to the equivalent 4.45 Gy acute dose. Micronuclei yields were measured at 24 h and 7 days using the in vitro cytokinesis-blocked micronucleus (CBMN) assay. The results showed that MNi yields increased up to 2.2 Gy with no further increase at 4.45 Gy and with no detectable dose-rate effect across the dose range 24 h or 7 days post exposure. In conclusion, the γ-H2AX biomarker showed higher sensitivity to measure dose-rate effects after low-dose LDR X rays compared to MNi formation; however, confounding factors such as variable repair times post exposure, increased cell killing and cell cycle block likely contributed to the yields of MNi with accumulating doses of ionizing radiation.

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Section: Introductionmentioning

confidence: 99%

Effect of Dose Rate on Residual γ-H2AX Levels and Frequency of Micronuclei in X-Irradiated Mouse Lymphocytes

et al. 2015

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“…Micronucleus frequency in lymphocytes exposed to low LET radiation such X-rays, gamma rays, and electron beams increases linearly-quadratically with the absorbed dose, indicating a contribution of both single and multi-track lesions (16,25,26). Therefore, MN frequency is clearly infl uenced by dose rates.…”

Section: Discussionmentioning

confidence: 99%

“…Many studies have shown remarkable variation in biological damages with pulse frequency. Bellucci (31) showed that 20 pulses per second was the most lethal dose rate for cells in the pulse range of four to 24 pulses per second, while Hood and Norris (32) found no variations in lethality of normal and malignant human cells exposed to pulsed X-ray in the wide range of 1x10 5 to 3x10 5 pulses per minute. A signifi cant depletion in oxygen concentration was demonstrated when doses were given in a single pulse.…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, MN in cytokinesis-blocked binucleated lymphocytes have been used to quantitatively assess the absorbed dose in cases of suspected radiation exposure and situations involving radiation accidents (3). The dose-response curve of MN frequency in peripheral blood lymphocytes induced by low linearenergy-transfer (LET) radiations is best described by linear-quadratic function (4)(5)(6)(7). The slope of the dose-response curve, which represents a numerical measure of aberrations induced by single radiation track events, is usually independent of the dose rate.…”

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confidence: 99%

“…Several earlier studies have suggested that even though it is quite obvious that radiobiological damage decreases with the dose rate, this does not work the other way around when the dose rate rises above a certain level (5,(9)(10)(11). However, there are conflicting reports regarding the dose rate effect studied in different types of cells (12)(13)(14)(15).…”

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Dose Rate Effect of Pulsed Electron Beam on Micronucleus Frequency in Human Peripheral Blood Lymphocytes

Acharya

Sanjeev

Bhat

et al. 2010

Archives of Industrial Hygiene and Toxicology

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The micronucleus assay in human peripheral blood lymphocytes is a sensitive indicator of radiation damage and could serve as a biological dosimeter in evaluating suspected overexposure to ionising radiation. Micronucleus (MN) frequency as a measure of chromosomal damage has also extensively been employed to quantify the effects of radiation dose rate on biological systems. Here we studied the effects of 8 MeV pulsed electron beam emitted by Microtron electron accelerator on MN induction at dose rates between 35 Gy min -1 and 352.5 Gy min -1 . These dose rates were achieved by varying the pulse repetition rate (PRR). Fricke dosimeter was employed to measure the absorbed dose at different PRR and to ensure uniform dose distribution of the electron beam. To study the dose rate effect, blood samples were irradiated to an absorbed dose of (4.7±0.2) Gy at different rates and cytogenetic damage was quantifi ed using the micronucleus assay. The obtained MN frequency showed no dose rate dependence within the studied dose rate range. Our earlier dose effect study using 8 MeV electrons revealed that the response of MN was linear-quadratic. Therefore, in the event of an accident, dose estimation can be made using linear-quadratic dose response parameters, without adding dose rate as a correction factor. Arh Hig Rada Toksikol 2010;61:77-83 The micronucleus (MN) assay has been suggested as a reliable alternative method to scoring chromosome aberrations such as dicentrics and rings (1, 2). It allows for the screening of much larger numbers of cells. Furthermore, MN in cytokinesis-blocked binucleated lymphocytes have been used to quantitatively assess the absorbed dose in cases of suspected radiation exposure and situations involving radiation accidents (3). The dose-response curve of MN frequency in peripheral blood lymphocytes induced by low linearenergy-transfer (LET) radiations is best described by linear-quadratic function (4-7). The slope of the dose-response curve, which represents a numerical measure of aberrations induced by single radiation track events, is usually independent of the dose rate. KEY WORDS: dosimetry, microtron, 8 MeV electrons, pulse repetition rate Acharya S, et al. PULSED ELECTRON BEAM DOSE RATE EFFECT ON MN FREQUENCYThe quadratic component that refers to an interaction between effects from two or more independent tracks is dose rate dependent, and its magnitude depends on the time interval between the two tracks (8).The dose rate effect of radiation is a biophysical phenomenon and is a consequence of repair of sublethal damage. Several earlier studies have suggested that even though it is quite obvious that radiobiological damage decreases with the dose rate, this does not work the other way around when the dose rate rises above a certain level (5, 9-11). However, there are conflicting reports regarding the dose rate effect studied in different types of cells (12-15).Our earlier dose-effect study using 8 MeV electrons revealed that the response of MN was linear-quadratic Unauthenticated Download ...

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The effect of electron and gamma irradiation on the induction of micronuclei in cytokinesis-blocked human blood lymphocytes

Acharya

Sanjeev

Bhat

et al. 2009

Radiat Environ Biophys

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The effect of electrons and gamma irradiation on the induction of micronuclei in cytokinesis-blocked human peripheral blood lymphocytes was investigated to understand the relative biological effectiveness (RBE) of electrons compared with gamma rays. Blood samples were irradiated with an 8 MeV pulsed electron beam, at a mean instantaneous dose rate of 2.6 x 10(5) Gy s(-1). Gamma irradiation was carried out at a dose rate of 1.98 Gy min(-1) using (60)Co gamma source. A dose-dependent increase in micronuclei yield was observed. The dose-response relationships for induction of micronuclei fitted well to a linear-quadratic relationship and the coefficients alpha and beta of the dose-response curve were estimated by fitting the data using error-weighted minimum chi (2) method. The RBE of 8 MeV electrons were found to be near unity as compared with gamma rays.

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Dose rate effect on micronucleis induction in cytokinesis blocked human peripheral blood lymphocytes

Cited by 18 publications

References 0 publications

Effect of Dose Rate on Residual γ-H2AX Levels and Frequency of Micronuclei in X-Irradiated Mouse Lymphocytes

Effect of Dose Rate on Residual γ-H2AX Levels and Frequency of Micronuclei in X-Irradiated Mouse Lymphocytes

Dose Rate Effect of Pulsed Electron Beam on Micronucleus Frequency in Human Peripheral Blood Lymphocytes

The effect of electron and gamma irradiation on the induction of micronuclei in cytokinesis-blocked human blood lymphocytes

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