Evidence for Radiation Hormesis after In Vitro Exposure of Human Lymphocytes to Low Doses of Ionizing Radiation (original) (raw)
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Dose-Response, 2008
ᮀ Previous research has demonstrated that adding a very small gamma-ray dose to a small alpha radiation dose can completely suppress lung cancer induction by alpha radiation (a gamma-ray hormetic effect). Here we investigated the possibility of gamma-ray hormesis during low-dose neutron irradiation, since a small contribution to the total radiation dose from neutrons involves gamma rays. Using binucleated cells with micronuclei (micronucleated cells) among in vitro monoenergetic-neutron-irradiated human lymphocytes as a measure of residual damage, we investigated the influence of the small gammaray contribution to the dose on suppressing residual damage. We used residual damage data from previous experiments that involved neutrons with five different energies (0.22-, 0.44-, 1.5-, 5.9-, and 13.7-million electron volts [MeV]). Corresponding gamma-ray contributions to the dose were approximately 1%, 1%, 2%, 6%, and 6%, respectively. Total absorbed radiation doses were 0, 10, 50, and 100 mGy for each neutron source. We demonstrate for the first time a protective effect (reduced residual damage) of the small gamma-ray contribution to the neutron dose. Using similar data for exposure to gamma rays only, we also demonstrate a protective effect of 10 mGy (but not 50 or 100 mGy) related to reducing the frequency of micronucleated cells to below the spontaneous level.
Reports of Practical Oncology & Radiotherapy, 2005
Aim This investigation presents the estimation of cytogenetic injury in human peripheral blood lymphocytes and its dependence on the dose and quality of ionizing radiation applied in radiotherapy of cancer patients with the purpose of calculating RBE values for different radiation sources in the dose range under study. Materials/Methods Cytogenetic dosimetry was carried out at an exposure of human lymphocyte cultures to 137 Cs and 60 Co therapeutic sources and neutrons with average energies of 6 and 22 MeV. Results Increase in dose reduces RBE values of 137 Cs g-irradiation, which in the range of doses investigated (0.3-5.0 Gy) vary between 3.5-1.3, respectively. Thus the difference in RBE values can be most accurately determined in the 0.5-2.0 Gy dose interval usually used in radiotherapy. Comparative estimation of fast neutron RBE values showed that 6 MeV neutrons give signifi cantly higher yields of chromosome aberrations as compared with 22 Mev neutrons. It was shown that cytogenetic effectiveness has a tendency to decrease with the increase in the depth of the water phantom. The largest effect was observed at the depth of up to 6 cm. Conclusions The results of our pre-clinical studies indicate that radiation-induced effects simultaneously depend on different irradiation parameters such as dose, energy and the depth of the irradiated biological object, which should be taken into account in radiotherapy of cancer patients.
Micronuclei Induced by Fast Neutrons Versus 60 Co γ-rays in Human Peripheral Blood Lymphocytes
International Journal of Radiation Biology, 1994
Here we compared the effectiveness of neutrons (=5 .5MeV) versus 60 CO y-rays in producing micronuclei (MN) in human lymphocytes . To obtain dose-response data, blood samples of six donors were irradiated with doses ranging from 0 . 1 to 5 Gy for y-rays and 0 . 1-3 Gy for neutrons . A linear dependence of MN yield with dose was found for fast neutrons while for y-rays a nonlinear dependence existed . For both radiation qualities no significant interindividual differences were found . Derived relative biological effectiveness values decreased with increasing dose. The MN frequency distributions were overdispersed with respect to the Poisson distribution, with neutrons showing higher dispersion values than with y-rays . To compare the repair kinetics of both radiation qualities split-dose experiments were performed . A dose of 4 Gy grays (3 Gy neutrons) was delivered either as a single exposure or in two equal fractions separated by time intervals ranging from 30 min to 10h (30 min to 7 h for neutrons) . The data showed for y-rays a significant decline (30%±10%) in MN yield with interfraction time due to repair of DNA damage . This repair is a continuous process starting almost immediately after the first of the two doses and lasting 3-5 h . For fast neutrons no decline was observed indicating irreparable damage . Int J Radiat Biol Downloaded from informahealthcare.com by University of Maastricht on 11/23/12 For personal use only. Int J Radiat Biol Downloaded from informahealthcare.com by University of Maastricht on 11/23/12 For personal use only. Int J Radiat Biol Downloaded from informahealthcare.com by University of Maastricht on 11/23/12 For personal use only.
International Journal of Molecular Sciences
The lack of information on how biological systems respond to low-dose and low dose-rate exposures makes it difficult to accurately assess the carcinogenic risks. This is of critical importance to space radiation, which remains a serious concern for long-term manned space exploration. In this study, the γ-H2AX foci assay was used to follow DNA double-strand break (DSB) induction and repair following exposure to neutron irradiation, which is produced as secondary radiation in the space environment. Human lymphocytes were exposed to high dose-rate (HDR: 0.400 Gy/min) and low dose-rate (LDR: 0.015 Gy/min) p(66)/Be(40) neutrons. DNA DSB induction was investigated 30 min post exposure to neutron doses ranging from 0.125 to 2 Gy. Repair kinetics was studied at different time points after a 1 Gy neutron dose. Our results indicated that γ-H2AX foci formation was 40% higher at HDR exposure compared to LDR exposure. The maximum γ-H2AX foci levels decreased gradually to 1.65 ± 0.64 foci/cell (L...
Low-dose irradiation alters the radio-sensitivity of human peripheral blood lymphocytes
IFMBE Proceedings, 2013
DNA is the most critical target of ionizing radiation when interact with cells. Several molecular studies have demonstrated modifications in expression levels of genes involved in the processes of signal transduction, cell cycle control, DNA repair and apoptosis following to exposure to ionizing radiation. The apoptosis intrinsic pathway is the main pathway that leads to apoptosis in response to DNA damage. The latter is responsible to regulate the release of mitochondrial proteins, including cytochrome-c (cytc). The aim of this study was to evaluate role of low-doses of gamma radiation on the apoptotic genes expression in human peripheral blood lymphocytes. Mononuclear cells were isolated from whole blood samples. They were exposed in culture to different doses from 2 to 10 cGy by gamma rays from a cobalt-60 source. Two apoptotic genes; BAX (pro-apoptotic) and Bcl-2 (antiapoptotic) were examined by relative quantitative Real-Time PCR for expression level, 4 and 24 hours following to irradiation. The study revealed, low doses of gamma radiation induced down-regulation for BAX gene and up-regulation for Bcl-2 gene. The result of present study has showed that low doses of gamma radiation could increase Bcl-2/BAX ratio and radio-resistance. These findings suggest that the genotoxic effects of low doses of gamma radiation may be due to adaptive response and a reduction of apoptosis.
International Journal of Radiation Oncology*Biology*Physics, 2000
Purpose: Changes in the sensitivity of intratumor quiescent (Q) and total cells to ␥-rays following thermal neutron irradiation with or without 10 B-compound were examined. Methods and Materials: 5-Bromo-2-deoxyuridine (BrdU) was injected to SCC VII tumor-bearing mice intraperitoneally 10 times to label all the proliferating (P) tumor cells. As priming irradiation, thermal neutrons alone or thermal neutrons with 10 B-labeled sodium borocaptate (BSH) or dl-p-boronophenylalanine (BPA) were administered. The tumor-bearing mice then received a series of ␥-ray radiation doses, 0 through 24 h after the priming irradiation. During this period, no BrdU was administered. Immediately after the second irradiation, the tumors were excised, minced, and trypsinized. Following incubation of tumor cells with cytokinesis blocker, the micronucleus (MN) frequency in cells without BrdU labeling ؍( Q cells at the time of priming irradiation) was determined using immunofluorescence staining for BrdU. The MN frequency in the total (P ؉ Q) tumor cells was determined from the tumors that were not pretreated with BrdU before the priming irradiation. To determine the BrdU-labeled cell ratios in the tumors at the time of the second irradiation, each group also included mice that were continuously administered BrdU until just before the second irradiation using mini-osmotic pumps which had been implanted subcutaneously 5 days before the priming irradiation. Results: In total cells, during the interval between the two irradiations, the tumor sensitivity to ␥-rays relative to that immediately after priming irradiation decreased with the priming irradiation ranking in the following order: thermal neutrons only > thermal neutrons with BSH > thermal neutrons with BPA. In contrast, in Q cells, during that time the sensitivity increased in the following order: thermal neutrons only < thermal neutrons with BSH < thermal neutrons with BPA. The longer the interval between the two irradiations, the higher was the BrdU-labeled cell ratio at the second irradiation. The labeled cell ratio at the same time point after each priming irradiation increased in the following order: thermal neutrons only < thermal neutrons with BSH < thermal neutrons with BPA. Conclusion: These findings indicated that the use of 10 B-compound, especially BPA, in thermal neutron irradiation causes the recruitment from the Q to P population.
Micronuclei induction in human fibroblasts exposed in vitro to Los Alamos high-energy neutrons
Advances in Space Research, 2007
High-energy secondary neutrons, produced by the interaction of galactic cosmic rays with the atmosphere, spacecraft structure and planetary surfaces, contribute to a significant fraction to the dose equivalent in crew members and passengers during commercial aviation travel, and astronauts in space missions. The Los Alamos Nuclear Science Center (LANSCE) neutron facility's ICE House 30L beamline is known to generate neutrons that simulate the secondary neutron spectra of earth's atmosphere. The neutron spectrum is also similar to that measured onboard spacecraft like the MIR and International Space Station (ISS). To evaluate the biological damage, we exposed human fibroblasts in vitro to the LANSCE neutron beams without degrader at an entrance dose rate of 25 mGy/hr and analyzed the micronuclei (MN) induction. The cells were also placed behind a 9.9 cm water column to study effect of shielding in the protection of neutron induced damages. It was found that the dose response in the MN frequency was linear for the samples with and without shielding and the slope of the MN yield behind the shielding was reduced by a factor of 3.5. Compared to the MN induction in human fibroblasts exposed to a γ source at a low dose rate, the RBE was found to be 16.7 and 10.0 for the neutrons without and with 9.9 cm water shielding, respectively. 155, 353-9 (2001).
The quantification of micronuclei in lymphocytes is a method for estimating of individual exposure to ionizing radiation, which can be used complementary to physical dosimetry or when this later cannot be performed. In this work, the quantification of micronuclei was carried out using cytogenetic analyzes of peripheral blood samples from 5 patients with cervical uterine cancer following radiotherapy, in order to evaluate the absorbed dose as a result of exposure to 60 Co source. From each patient, blood samples were collected in three phases of the treatment: before irradiation, 24 h after receiving 0.08 Gy and 1.8 Gy, respectively. A good agreement was obtained between doses estimated by calibration curve of dose versus the frequencies of micronuclei and the values previously planned to the radiotherapy. The results presented in this report emphasizes biological dosimetry, based on the quantification of micronuclei in lymphocytes from peripheral blood, as an important methodology f...
Evaluation of the cytotoxicity and the genotoxicity induced by α radiation in an A549 cell line
Radiation Measurements, 2011
Exposure to radon and its progenies represents one of the greatest risks of ionizing radiation from natural sources. Nowadays, these risks are assessed by the extrapolation of biological effects observed from epidemiological data. In the present study, we made a dose response curve, to evaluate the in vitro response of A549 human lung cells to a-radiation resulting from the decay of a 210 Po source, evaluated by the cytokinesis blocked micronuclei assay. The clonogenic assay was used to measure the survival cell fraction. As expected, the results revealed an increase of cellular damage with increased doses made evident from the increased number of micronuclei (MN) per binucleated cell (BN). Besides this study involving the biological effects induced by direct irradiation, and due to the fact that radiation-induced genomic instability is thought to be an early event in radiation carcinogenesis, we analyzed the genomic instability in early and delayed untargeted effects, by using the medium transfer technique. The obtained results show that unirradiated cells exposed to irradiated medium reveal a higher cellular damage in earlier effects when compared to the delayed effects. The obtained results may provide clues for the biodosimetric determination of radon dose to airway cells at cumulative exposures.