CONSTRUCTION AND VALIDATION OF IN VITRO DOSE–RESPONSE CALIBRATION CURVE USING DICENTRIC CHROMOSOME ABERRATION

2020 ◽  
Vol 189 (2) ◽  
pp. 198-204
Author(s):  
Ehsan Mirrezaei ◽  
Saeed Setayeshi ◽  
Farideh Zakeri ◽  
Samaneh Baradaran
Keyword(s):  
Dose Response ◽  
Calibration Curve ◽  
Radiation Effects ◽  
Standard Dose ◽  
Absorbed Dose ◽  
Dicentric Chromosome ◽  
Blood Samples ◽  
Radiation Induced ◽  
Occupational Radiation

Abstract Cytogenetic biodosimetry is a well-known method for quantifying the absorbed dose based on measuring biological radiation effects. To correlate the induced chromosomal abberrations with the absorbed dose of the individuals, a reliable dose–response calibration curve should be established. This study aimed to use frequencies and distributions of radiation-induced dicentric chromosome aberrations to develop a standard dose–response calibration curve. Peripheral blood samples taken from six male donors irradiated by an X-ray generator up to 4 Gy were studied. Three different blood samples were irradiated by known doses, then scored blindly for verification of the proposed calibration curve. Dose estimation was also carried out for three real overexposed cases. The results showed good accordance with the other published curves. The constructed dose–response curve provides a reliable tool for biological dosimetry in accidental or occupational radiation exposures.

scholarly journals Establishing a Reference Dose–Response Calibration Curve for Dicentric Chromosome Aberrations to Assess Accidental Radiation Exposure in Saudi Arabia

2020 ◽  
Vol 8 ◽  
Author(s):  
Ghazi A. Alsbeih ◽  
Khaled S. Al-Hadyan ◽  
Najla M. Al-Harbi ◽  
Sara S. Bin Judia ◽  
Belal A. Moftah
Keyword(s):  
Radiation Exposure ◽  
Dose Response ◽  
Calibration Curve ◽  
Goodness Of Fit ◽  
Dicentric Chromosome ◽  
Homogeneity Test ◽  
X Rays ◽  
Blood Samples ◽  
Reference Dose ◽  
Effect Of Age

In cases of nuclear and radiological accidents, public health and emergency response need to assess the magnitude of radiation exposure regardless of whether they arise from disaster, negligence, or deliberate act. Here we report the establishment of a national reference dose–response calibration curve (DRCC) for dicentric chromosome (DC), prerequisite to assess radiation doses received in accidental exposures. Peripheral blood samples were collected from 10 volunteers (aged 20–40 years, median = 29 years) of both sexes (three females and seven males). Blood samples, cytogenetic preparation, and analysis followed the International Atomic Energy Agency EPR-Biodosimetry 2011 report. Irradiations were performed using 320 kVp X-rays. Metafer system was used for automated and assisted (elimination of false-positives and inclusion of true-positives) metaphases findings and DC scoring. DC yields were fit to a linear–quadratic model. Results of the assisted DRCC showed some variations among individuals that were not statistically significant (homogeneity test, P = 0.66). There was no effect of age or sex (P > 0.05). To obtain representative national DRCC, data of all volunteers were pooled together and analyzed. The fitted parameters of the radiation-induced DC curve were as follows: Y = 0.0020 (±0.0002) + 0.0369 (±0.0019) *D + 0.0689 (±0.0009) *D2. The high significance of the fitted coefficients (z-test, P < 0.0001), along with the close to 1.0 p-value of the Poisson-based goodness of fit (χ2 = 3.51, degrees of freedom = 7, P = 0.83), indicated excellent fitting with no trend toward lack of fit. The curve was in the middle range of DRCCs published in other populations. The automated DRCC over and under estimated DCs at low (<1 Gy) and high (>2 Gy) doses, respectively, with a significant lack of goodness of fit (P < 0.0001). In conclusion, we have established the reference DRCC for DCs induced by 320 kVp X-rays. There was no effect of age or sex in this cohort of 10 young adults. Although the calibration curve obtained by the automated (unsupervised) scoring misrepresented dicentric yields at low and high doses, it can potentially be useful for triage mode to segregate between false-positive and near 2-Gy exposures from seriously irradiated individuals who require hospitalization.

scholarly journals EANM position paper on the role of radiobiology in nuclear medicine

2021 ◽  
Author(s):  
An Aerts ◽  
Uta Eberlein ◽  
Sören Holm ◽  
Roland Hustinx ◽  
Mark Konijnenberg ◽  
...  
Keyword(s):  
Nuclear Medicine ◽  
Absorbed Dose ◽  
Added Value ◽  
External Irradiation ◽  
Executive Summary ◽  
Dose Rates ◽  
Biological Responses ◽  
Medical Physicists ◽  
Radiation Induced

Executive SummaryWith an increasing variety of radiopharmaceuticals for diagnostic or therapeutic nuclear medicine as valuable diagnostic or treatment option, radiobiology plays an important role in supporting optimizations. This comprises particularly safety and efficacy of radionuclide therapies, specifically tailored to each patient. As absorbed dose rates and absorbed dose distributions in space and time are very different between external irradiation and systemic radionuclide exposure, distinct radiation-induced biological responses are expected in nuclear medicine, which need to be explored. This calls for a dedicated nuclear medicine radiobiology. Radiobiology findings and absorbed dose measurements will enable an improved estimation and prediction of efficacy and adverse effects. Moreover, a better understanding on the fundamental biological mechanisms underlying tumor and normal tissue responses will help to identify predictive and prognostic biomarkers as well as biomarkers for treatment follow-up. In addition, radiobiology can form the basis for the development of radiosensitizing strategies and radioprotectant agents. Thus, EANM believes that, beyond in vitro and preclinical evaluations, radiobiology will bring important added value to clinical studies and to clinical teams. Therefore, EANM strongly supports active collaboration between radiochemists, radiopharmacists, radiobiologists, medical physicists, and physicians to foster research toward precision nuclear medicine.

scholarly journals Spectrophotometric Study of ?-Irradiated PM-355

2009 ◽  
Vol 6 (3) ◽  
pp. 584-589
Author(s):  
Baghdad Science Journal
Keyword(s):  
Absorption Spectra ◽  
Calibration Curve ◽  
Linear Relation ◽  
Response Curve ◽  
Energy Gap ◽  
Linear Part ◽  
Absorbed Dose ◽  
Spectrophotometric Study ◽  
High Dose ◽  
Radiation Induced

The aim of the present work is concerned with the effect of ?-irradiation on PM-355 with absorbed dose of (30-160Mrad) range. This polymer is evaluated spectrophotometrically for use as high dose dosimeters. The absorption spectra of irradiated samples showed radiation induced absorption changes. There is an increment in absorption proportional with absorbed dose. This increment is attributed to interfaces traps which, are formed by irradiation. Calibration curve was drawn .The linear relation was found in calibration curve, and dosimeter range was determined from the linear part. The linearity in response curve suggested that PM-355 could be used as dosimeter within (30-160Mrad) rang. Energy gap shift was used as a second tool to determine the dosimeter range. It was found that PM-355 energy gap systematically decreasing with absorbed dose, and it could be used as a second tool to determine the dosimeter range.

scholarly journals Differential Regulation of Ferritin Subunits and Iron Transport Proteins: An Effect of Targeted Hepatic X-Irradiation

2013 ◽  
Vol 2013 ◽  
pp. 1-8 ◽  
Author(s):  
Naila Naz ◽  
Shakil Ahmad ◽  
Silke Cameron ◽  
Federico Moriconi ◽  
Margret Rave-Fränk ◽  
...  
Keyword(s):  
Radiation Effects ◽  
Complete Blood Count ◽  
Mrna Level ◽  
Isolated Hepatocytes ◽  
Serum Marker ◽  
Neutrophil Granulocytes ◽  
Early Increase ◽  
Radiation Induced

The current study aimed to investigate radiation-induced regulation of iron proteins including ferritin subunits in rats. Rat livers were selectively irradiatedin vivoat 25 Gy. This dose can be used to model radiation effects to the liver without inducing overt radiation-induced liver disease. Sham-irradiated rats served as controls. Isolated hepatocytes were irradiated at 8 Gy. Ferritin light polypeptide (FTL) was detectable in the serum of sham-irradiated rats with an increase after irradiation. Liver irradiation increased hepatic protein expression of both ferritin subunits. A rather early increase (3 h) was observed for hepatic TfR1 and Fpn-1 followed by a decrease at 12 h. The increase in TfR2 persisted over the observed time. Parallel to the elevation of AST levels, a significant increase (24 h) in hepatic iron content was measured. Complete blood count analysis showed a significant decrease in leukocyte number with an early increase in neutrophil granulocytes and a decrease in lymphocytes.In vitro, a significant increase in ferritin subunits at mRNA level was detected after irradiation which was further induced with a combination treatment of irradiation and acute phase cytokine. Irradiation can directly alter the expression of ferritin subunits and this response can be strongly influenced by radiation-induced proinflammatory cytokines. FTL can be used as a serum marker for early phase radiation-induced liver damage.

scholarly journals DNA Damage in Blood Leukocytes of Prostate Cancer Patients Undergoing PET/CT Examinations with [68Ga]Ga-PSMA I&T

Cancers ◽  
2020 ◽  
Vol 12 (2) ◽  
pp. 388 ◽  
Author(s):  
Sarah Schumann ◽  
Harry Scherthan ◽  
Torsten Frank ◽  
Constantin Lapa ◽  
Jessica Müller ◽  
...  
Keyword(s):  
Contrast Agent ◽  
Ex Vivo ◽  
Absorbed Dose ◽  
Dna Double Strand Breaks ◽  
Blood Leukocytes ◽  
Blood Samples ◽  
Time Points ◽  
Pet Ct ◽  
Radiation Induced

The aim was to investigate the induction and repair of radiation-induced DNA double-strand breaks (DSBs) as a function of the absorbed dose to the blood of patients undergoing PET/CT examinations with [68Ga]Ga-PSMA. Blood samples were collected from 15 patients before and at four time points after [68Ga]Ga-PSMA administration, both before and after the PET/CT scan. Absorbed doses to the blood were calculated. In addition, blood samples with/without contrast agent from five volunteers were irradiated ex vivo by CT while measuring the absorbed dose. Leukocytes were isolated, fixed, and stained for co-localizing γ-H2AX+53BP1 DSB foci that were enumerated manually. In vivo, a significant increase in γ-H2AX+53BP1 foci compared to baseline was observed at all time points after administration, although the absorbed dose to the blood by 68Ga was below 4 mGy. Ex vivo, the increase in radiation-induced foci depended on the absorbed dose and the presence of contrast agent, which could have caused a dose enhancement. The CT-dose contribution for the patients was estimated at about 12 mGy using the ex vivo calibration. The additional number of DSB foci induced by CT, however, was comparable to the one induced by 68Ga. The significantly increased foci numbers after [68Ga]Ga-PSMA administration may suggest a possible low-dose hypersensitivity.

scholarly journals Development of dose-response calibration curve for dicentric chromosome induced by X-rays

2019 ◽  
Vol 10 (1) ◽  
pp. 2 ◽  
Author(s):  
Yanti Lusiyanti ◽  
Mukh Syaifudin ◽  
Tuti Budiantari ◽  
Sofiati Purnami ◽  
Dwi Ramadhani
Keyword(s):  
Dose Response ◽  
Calibration Curve ◽  
Dicentric Chromosome ◽  
X Rays

Radiation induced chromosome aberrations in human foetal cells grown in vitro

1962 ◽  
Vol 11 (4) ◽  
pp. 356-389 ◽  
Author(s):  
J. A. Böök ◽  
M. Fraccaro ◽  
K. Fredga ◽  
J. Lindsten
Keyword(s):  
Brain Tissue ◽  
Cell Cultures ◽  
Lung Tissue ◽  
Cultured Cells ◽  
Absorbed Dose ◽  
Cell Populations ◽  
Foetal Brain ◽  
Radiation Induced ◽  
Foetal Lung

SUMMARYThe effect of ionizing radiation, from a 100 Curie Cobalt-60 source, on diploid human cells grown in vitro has been investigated.The analysed cell populations originated from foetal brain and lung tissue. Other known variations of this material were age and sex of the foetuses, primary and first transfer cultures.The effect was measured by recording post-metaphase chromosomal aberrations in cell cultures fixed and stained 24 and 48 hours after acute irradiation. “Spontaneous” aberration frequencies were determined in matched control cultures.Although conclusions must be guarded, in view of the insufficient knowledge of factors influencing human cell populations in vitro, our observations can be summarized, tentatively, in the following main points.1. The frequency of “spontaneous” aberrations appears to vary with respect to (a) differences between the individuals from whom the biopsies were taken, (b) tissue of origin whether within or between individuals and (c) the sex of the cultured cells.The qualified estimates of the overall averages of “spontaneous” aberrations were, (a) for the cell cultures derived from foetal lung 0.7 per cent (41/5,891 scored cells) and (b) for the cell cultures derived from foetal brain 2.5 per cent (21/851 scored cells).2. In the irradiated cell cultures which received doses varying from 9-136 rads of absorbed dose the number of aberrant post-metaphases per 100 cells per rad varied from 0.10-0.15 for cultures derived from lung tissue and from 0.19-0.37 for cultures derived from brain tissue, all at 24 hours after the acute dose. At 48 hours after irradiation the frequencies were somewhat lower but the same trends remained.3. The cell cultures derived from brain tissue appear to have a higher radio-sensitivity than those derived from lung tissue. Furthermore, a sexual dimorphism is suggested because, in all series of cultures, those composed of XY cells had a higher aberration frequency as compared to those with XX cells.4. The irradiation doubling dose (for definition, see p. 27) was estimated at 15-40 rads (cf. table 7).

scholarly journals The Double Threshold: Consequences for Identifying Low-Dose Radiation Effects

Dose-Response ◽  
2020 ◽  
Vol 18 (3) ◽  
pp. 155932582094972
Author(s):  
Alan Waltar ◽  
Ludwig Feinendegen
Keyword(s):  
Dose Response ◽  
Radiation Effects ◽  
Low Dose ◽  
Development Program ◽  
Absorbed Dose ◽  
Current Data ◽  
Whole Body ◽  
Radiation Quality ◽  
Adaptive Protection ◽  
New Research

Prior to observing low-dose-induced cell signaling and adaptive protection, radiogenic stochastic effects were assumed to be linearly related to absorbed dose. Now, abundant data prove the occurrence of radiogenic adaptive protection specifically at doses below ∼ 200 mGy (with some data suggesting such protection at a dose even higher than 200 mGy). Moreover, cells do not thrive properly when deprived of radiation below background dose. Two threshold doses need be considered in constructing a valid dose-response relationship. With doses beginning to rise from zero, cells increasingly escape radiation deprivation. The dose at which radiation-deprived cells begin to function homeostatically provides dose Threshold A. With further dose increase, adaptive protection becomes prominent and then largely disappears at acute doses above ∼ 200 mGy. The dose at which damage begins to override protection defines Threshold B. Thresholds A and B should be terms in modeling dose-response functions. Regarding whole-body responses, current data suggest for low-LET acute, non-chronic, irradiation a Threshold B of about 100 mGy prevails, except for leukemia and probably some other malignancies, and for chronic, low dose-rate irradiation where the Threshold B may well reach 1 Gy per year. A new Research and Development Program should determine individual Thresholds A and B for various radiogenic cell responses depending on radiation quality and target.

scholarly journals Cellular Redox Status Regulates Emodin-Induced Radiosensitization of Nasopharyngeal Carcinoma Cells In Vitro and In Vivo

2013 ◽  
Vol 2013 ◽  
pp. 1-8 ◽  
Author(s):  
Huaxin Hou ◽  
Danrong Li ◽  
Daohai Cheng ◽  
Li Li ◽  
Ying Liu ◽  
...  
Keyword(s):  
Nasopharyngeal Carcinoma ◽  
Radiation Effects ◽  
Redox Status ◽  
Ros Generation ◽  
Cellular Redox ◽  
Hypoxic Conditions ◽  
M Phase ◽  
Radiation Induced

Here, we report that regulation of cellular redox status is required for radiosensitization of nasopharyngeal carcinoma (NPC) cells by emodin. We evaluated emodin’s radiosensitivity-enhancing ability by using NPC cells in vitro and xenografts in vivo. A clonogenic assay was performed to evaluate NPC cell survival and to determine dose modification factors. Flow cytometry, western blot analysis, and in vivo radiation-induced tumor regrowth delay assays were performed to characterize emodin’s effects. Exposure of CNE-1 NPC cells to emodin enhanced their radiosensitivity. HIF-1α expression significantly increased under hypoxic conditions but did not change after treatment with emodin alone. Emodin downregulated mRNA and protein expression of HIF-1α. Cells exposed to radiation and emodin underwent significant cell cycle arrest at the G2/M phase. The percentage of apoptotic cells and reactive oxygen species (ROS) levels were significantly higher in the group exposed to emodin and radiation hypoxic group than in the other groups. Compared to the CNE-1 xenografts exposed to radiation alone, CNE-1 xenografts exposed to radiation with emodin showed significantly enhanced radiation effects. Our data suggest that emodin effectively enhanced the radiosensitivity of CNE-1 cells in vitro and in vivo. The mechanism appears to involve ROS generation and ROS-mediated inhibition of HIF-1α expression.

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