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Background : There are growing evidences for chromosomal radioadaptive response in human lymphocytes . Highly variable inter- and intra-individual responses have been reported. Some individuals are non-responders and even in some donors the frequency of chromatid aberrations induced by a challenge dose increases by pre-exposure to an adapting dose. It has been proposed that the lack of radioadaptive response is due to transient physiological factors.

Materials and Methods : We found a young healthy donor who exhibited no radioadaptive response in our initial experiments. After a common adapting dose, the donor occasionally showed a highly increased susceptibility to subsequent high-dose irradiation. To assess whether the lack of radioadaptive response and the induction of a synergistic effect are transient responses , we have performed a 3-year follow-up study employing micronuclei in binucleated cells besides chromatid aberrations as biological endpoints. To eliminate the effect of the cell cycle on intrinsic radiosensitivity of a cell, we used the multiple-fixation regimen for analysis of chromosomal aberrations.

Results : This donor showed no adaptive response in any experiment.

Conclusion : Considering the consistent non-responsiveness observed throughout our serial experiments, it may be concluded that the lack of radioadaptive response is not attributed to some transient physiological factors but rather to permanent constitutional traits. Iran. J. Radiat. Res., 2003 1(1): 55 - 61.

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Background: Radioprotective capability of histamine H₂ receptor antagonists have been shown in several in vivo studies mainly using animal models. However, to verify the effectiveness of these agents in clinical applications, studies should be performed on human cells. In the present study radioprotective properties of these agents was examined in vitro on human lymphocytes using metaphase analysis.

Materials and Methods : In vitro metaphase analysis technique was used to test the effects of cimetidine, ranitidine and famotidine on radiation induced clastogenic effects. Lymphocytes in whole peripheral blood were exposed to 3 Gy gamma-rays at a dose rate of 73.7 cGy/min in the presence or absence of various doses of the drugs used in this study. The frequency of chromosomal aberrations were determined after standard metaphase preparations and staining slides in 5% Giemsa.

Results: Results show that radiation produced a high number of chromosomal aberrations in lymphocytes compared to controls (p<0.001). All three drugs used in this study effectively reduced the frequency of chromosomal aberrations at all doses. Famotidine was found to be more effective than the other two drugs.

Conclusion: From the results obtained it can be concluded that H ₂ -receptor antagonists used in this study effectively reduced the clastogenic effects of radiation with a dose reduction factor (DRF) of 1.5-2 in human lymphocytes in vitro. The way in which these drugs reduce the clastogenic effects of radiation might be via radical scavenging mechanism. Iran . J. Radiat. Res. 2003 1(2): 99 – 104.

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Background: Premature chromosome condensation (PCC) is a method for interphase chromosome analysis in biodosimetry. This study was performed to verify the usefulness of PCC induced by calyculin A in human peripheral blood lymphocytes (pbl) for biological dosimetry and possible construction of dose-response curve.

Materials and Methods: Peripheral blood was obtained from a healthy donor and exposed to various doses (0.25–4 Gy) of γ -rays. The frequency of simple breaks and dicentrics were scored in G2/M chromosomes of Giemsa stained cells.

Results: Results show that the frequency of simple chromosome breaks appears to increase linearly with dose while the frequency of dicentrics apparently increases linear-quadratically with the dose.

Conclusion: Induction of chromosome condensation by calyculin A is a powerful biodisimetric method, which provides a high number of spreads for analysis. With the use of this method, it is possible to overcome problems related to low mitotic index or cell-cycle alterations in routine metaphase analysis and low fusion rate in conventional PCC technique. Iran . J. Radiat. Res., 2004 2 (1): 15-20

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Background: Lymphocyte-dicentric assay is the most generally accepted method for biological dosimetry of overexposed individuals. In this study, the frequency of unstable chromosome
aberration in blood lymphocytes was used to estimate radiation dose received by individuals. Evaluation of dose using a calibration curve produced elsewhere may have a significant uncertainty therefore, experiments were performed to produce a dose-response curve using an
established protocol of international atomic energy agency.

Materials and Methods: Lymphocytes in whole peripheral blood obtained from healthy
individuals, were exposed to various doses of gamma radiation (0.25 – 4 Gy). Then after 1 hour of incubation in 37 ^oC, were cultured in complete RPMI-1640 medium. 500 mitoses were
analysed for the presence or absence of unstable chromosomal aberrations for each radiation dose after the standard metaphase preparation and staining slides.

Results and Conclusion: Intercellular distribution of dicentric chromosomes at each radiation dose has been used to contrast a dose-response curve. It seems that dose-effect relationship
follows with the linear-quadratic model. There is a good agreement between our dose-response curves with similar published studies by other laboratories. Iran . J. Radiat. Res., 2004 2 (2): 85-8 8

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  Background: A radioprotective effect of amifostine as well as its ability to modulate the level of spontaneous and gamma-irradiation-induced genetic changes on human peripheral blood lymphocytes has been investigated . Amifostine, known as a potent radical scavenger, has been introduced as the most effective radioprotector, yet it is not completely approved for the clinical use. However, further in vitro and clinical studies are needed to clarify its mechanisms of action.

  Materials and Methods : Whole blood samples from healthy donors were exposed to various doses of gamma-rays. Lymphocytes in cultures were treated with amifostine at different concentrations (2, 4 and 6 mM) in the presence or in the absence of 1 IU/ml alkaline phosphatase before or after gamma-irradiation. Standard procedure for the cytokinesis-block micronucleus (CBMN) assay was used to assess the effect of amifostine on radiation induced micronucleus in binucleate lymphocytes.

 

  Results : Irradiated blood samples showed an increase in the total number of micronuclei (MN) significantly different from controls (p<0.05). However, pre-treatment of lymphocytes with amifostine in the presence of alkaline phosphatase, 15 minutes before irradiation, led to a significant decrease in the frequencies of MN and cells with more than one MN (p<0.05). Amifostine, in its own, produced little or no protection. However, the addition of amifostine with alkaline phosphatase to the cell cultures 15 minutes after irradiation produced substantial radioprotection significantly different from the frequencies of MN induced by radiation alone (p<0.05).

  Conclusion : Results clearly indicated that gamma-rays induced MN in lymphocytes in a dose dependent manner. The highest protective effect was achieved when amifostine was phosphorilated by alkaline phosphatase and present before irradiation in the cellular environment, indicating its radical scavenging mechanism of radioprotection. Since the administration of amifostime after irradiation also led to a considerable decrease in the frequency of radiation induced MN, which might be possible for other mechanisms such as induction of cell cycle delay and hence influencing DNA repair, are involved in radioprotection by amifostine.

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Background: Boron and gadolinium are among the nuclides that hold a unique property of being a neutron capture therapy agent. Neutron beams have often a considerable portion of gamma rays with fast neutrons. Gamma rays, as beam contaminants, can cause considerable damage to normal tissues even if such tissues do contain high boron concentrations. Materials and Methods: The modification of radioresponse in human lymphocytes pretreated with boron or gadolinium compound was studied by assessing the DNA damage using single cell gel electrophoresis (SCGE), the comet assay. The lymphocytes from the human peripheral blood were irradiated with 0, 1, 2 and 4 Gy of gamma rays from a 60Co isotopic source with or without pretreatment of boron or gadolinium compound for 10 minutes at 4^oC. Post-irradiation procedures included slide preparation, cell-lysing, unwinding and electrophoresis, neutralization, staining, and analytic steps, gel electrophoresis. Results: The results indicate that pretreatment with boron compound (50 nM or 250 nM of 10B) is effective in reducing the radiosensitivity of the lymphocyte DNA. Conversely, pretreatment with gadolinium compound (50 nM) led to a dose-dependent increase in the radiosensitivity, most prominently with a dose of 4 Gy (P<0.001). Furthermore, when the lymphocytes were pretreated with a combined mixture (1:1) of boron (250 nM) and gadolinium (50 nM) compounds, the reduced radiosensitivity was also observed. Iran. J. Radiat. Res., 2009 7 (2): 63-68

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Background: The aim of preliminary study was determined development process status of T-cell population lymphocytes in Ukrainian children after 22 years from Chernobyl accident for next feasibility study. Material and Method: 150 participants aged 6 to 16 years are included in three groups: Group I (n=65), 30 to 60 km from center accident at zone 3th, Group II (n=65) 60 to 90 km from same location at zone 4th and control group (n=20) from Kiev, 100 km from same location. Peripheral blood leukocytes from buffy coats were analyzed for T-lymphocytes population such as T-lymphocytes (CD3), T-helper (CD4) and T-cytotoxic (CD8) by roseting method using erythrocytes that conjugated with monoclonal antibody against CD3, CD4, and CD8 receptors then CD4/CD8 ratio were calculated. Results: Percentage of CD3 and CD4 in groups II and I decreased significantly in compared to control group at P<0.001. Percent of CD8 decreased significantly in group I compared to control group at P <0.001. CD4/ CD8 ratio decreased significantly in-group I comparison to control group at P=0.02. Leucocytes count in groups II and I have not changed significantly in comparison to control group (P=0.09,P=0.4) but in group II, it was significantly different in comparison to group I at P <0.008. Conclusion: Our data show that after 2 decade of Chernobyl accident, ionizing radiation may have affected the developmental processes of T-cell population. Iran. J. Radiat. Res., 2009 7 (3): 127-133

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Background: The purpose of this paper is to establish an easy and reliable biodosimeter protocol to evaluate the biological effects of proton beams. Materials and Methods: Human peripheral blood lymphocytes were irradiated using proton beams (LET: 34.6 keV μm−1), and the chromosome aberrations induced were analyzed using cytokinesis-blocked (CB) micronucleus (MN) assay. To determine the efficiency of MN assay in estimating the doses received by 50MeV proton beams and to monitor predicted dose of victims in accidental exposure, here we have evaluated the performance of MN analysis in a simulated situation after exposure with proton beams. Peripheral lymphocytes were irradiated by 50MeV proton beams up to 6Gy and analyzed by Giemsa staining of CB MN assay. Results: The detected MN was found to be a significant dose-effect curve in the manner of dose-dependent increase after exposure with proton beams in vitro. When plotting on a linear scale against radiation dose, the line of best fit was Y=0.004+(1.882x10^-2±9.701x10^-5) D+(1.43x10^-3±1.571x10^-5)D2. Our results show a trend towards increase of the number of MN with increasing dose. It was linear-quadratic and has a significant relationship between the frequencies of MN and dose (R2= 0.9996). The number of MN in lymphocyte that was observed in control group is 5.202±0.04/cell. Conclusion: Hence, this simple protocol will be particularly useful for helping physicians to decide medical therapy for the initial treatment of victims with rapid and precise dose estimation after accidental radiation exposure. Also it has potential for use as a valuable biomarker to evaluate the biological effectiveness for cancer therapy with proton beams. Iran. J. Radiat. Res., 2011 8(4): 231-236

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Background: Chromosomal alterations play an important role in carcinogenesis. Enhanced chromosomal radiosensitivity is shown for many cancer predisposition conditions including breast cancer. In this study chromosomal radiosensitivity and the frequency of background sister chromnatid exchanges (SCE) in lymphocytes of normal individuals and breast cancer patients was compared. Materials and Methods: G₂ assay was performed on peripheral blood lymphocytes obtained from 60 breast cancer patients and 50 normal control. Blood culture was initiated and cells were irradiated with 1 Gy gammarays 4 h prior to harvesting. After metaphase preparations and slide making, chromatid aberrations were scored. For SCE studies, blood samples from 30 breast cancer patients and 30 normal control were studied. 24 hours after culture initiation, 5- bromodeoxy uridine (BrdU) was added and cells were harvested 48 hours after addition of BrdU. Slides were stained in Hoechst 33258 and exposed to UVA source, then stained in Giemsa. Results: Results indicated that the frequency of radiation induced chromatid breaks was significantly higher in breast cancer patients compared to normal control (p<0.01). From radiosensitivity point of view, 12% of normal control and 47% of breast cancer patients showed elevated chromatid radiosensitivity. Frequency of background SCE was significantly higher in lymphocytes of breast cancer patients compared to lymphocytes of control (p<0.05). Conclusion: Elevated chromosomal radiosensitivity and higher frequency of SCE in lymphocytes of breast cancer patients might be indicative of genomic instability of these cells. Increased radiosensitivity could also be due to defects in DNA repair genes involved in breast cancer formation. Iran. J. Radiat. Res., 2011 9(3): 167-174

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Background: Medical diagnostic procedures such as X-ray and computed Tomography (CT) scan account for considerable percent of patient's exposure to ionizing radiation. The exposure of cells to Ionization radiation results in induction of DNA damage and chromosomal aberrations. Contrast media (CM) are widely used in diagnostic radiology and CT scan. The aim of this study was to study adverse genetic effects of combined administration of non ionic contrast media and low dose X-rays in peripheral blood Lymphocytes of patients following abdominal CT scan. Materials and Methods: A total of 55 patients underwent abdominal CT scan with injection of non ionic contrast media (30 patients with omnipaque 300 mg/ml and 25 patients with visipaque 270 mg/ml) as well as 13 patients undergoing abdominal CT scan (without contrast), selected as control group, were enrolled in this study. Peripheral blood leukocytes were obtained in heparin containing tubes and cultured for the micronucleus test, or were directly used for apoptosis and DNA damage with the neutral comet assay. Results: The frequency of micronuclei, apoptosis and percentage of DNA damage was increased in most patients after the injection of contrast media, significantly different from the control group as compared with the samples obtained before and after injection of contrast media (P<0.05). Conclusion: The present study suggest that non ionic contrast media (omnipaque 300 mg/ml and visipaque 270 mg/ml) may cause a significant increase of cytogenetic damage in peripheral blood lymphocytes. This effect might be caused by the enhancement of radiation dose by CM that eventually may lead to the manifestation of ill health such as cancer.