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Development of dose-response calibration curve for dicentric chromosome induced by X-rays
Yanti Lusiyanti, Mukh Syaifudin, Tuti Budiantari, Sofiati Purnami, Dwi Ramadhani
January-December 2019, 10(1):2-2
DOI:10.4103/genint.genint_1_19  PMID:31391915
Chromosome aberration is a biomarker that has been used as a standard tool in biological dosimetry (biodosimetry) of individuals after exposure to ionizing radiation. It is based mainly on the induction of dicentric chromosomes – one of the radiation-induced biological effects, in order to correlate them with radiation dose. In this study, a dose calibration curve for X-rays was generated by using the dicentric assay and by fitting the data to both Chromosomal Aberration Calculation Software and Dose Estimate programs to compare the output of each method. Peripheral blood samples from four nonsmoker healthy donors were irradiated with various doses ranging from 0 to 4 Gy with 250 kV or 122 keV X-rays at a dose rate of 0.17 Gy/min. The irradiated blood was cultured, harvested, and analyzed according to the standard procedure as described by the International Atomic Energy Agency with slight modifications. The dose-response calibration data for dicentrics were fitted with the linear-quadratic model (Ydic = 0.03987D2 + 0.00651D). The dose-response calibration curve obtained in this research was comparable to other estimations with similar radiation quality and dose rates. The results in this research convinced us in sustaining a biodosimetry using a dose-response calibration curve in our laboratory.
  8,517 701 6
Systematic analysis of integrated gene functional network of four chronic stress-related lifestyle disorders
Souvick Roy, Abhik Chakraborty, Chinmoy Ghosh, Birendranath Banerjee
January-December 2015, 6(1):1-1
Background: Stress is a term used to define factors involved in changes in the physiological balances resulting in disease conditions. Chronic exposure to stress conditions in modern lifestyles has resulted in a group of disorders called lifestyle disorders. Genetic background and environmental factors are interrelated to lifestyle in determining the health status of individuals. Hence, identification of disease-associated genes is the primary step toward explanations of pathogenesis of these diseases. In functional genomics, large-scale molecular and physiological data are used for the identification of causative genes associated with a disease. Aim: The objective of our study was to find a common set of genes involved in chronic stress-related lifestyle diseases such as cardiovascular diseases (CVDs), type 2 diabetes (T2D), hypertension (HTN), and obesity. Materials and Methods: In our study, we have performed a systematic analysis of the functional gene network of four chronic stress-related lifestyle diseases by retrieving genes from published databases. We have tried to systematically construct a functional protein-protein interaction (PPI) network. The goals of establishing this network were the functional enrichment study of interacting partners as well as functional disease ontology annotation (FunDO) of the enriched genes. Results: This study enabled the identification of key genes involved in these stress-related lifestyle diseases by prioritizing candidate genes based on their degree of involvement. In this systematic analysis, we have found key genes for these diseases based on their involvement and association at the gene network level and PPI. Conclusion: We have deciphered a group of genes that in combination play a crucial role and may impact the function of the whole genome in the four lifestyle disorders mentioned.
  7,662 455 4
Involvement of iron-containing proteins in genome integrity in arabidopsis thaliana
Caiguo Zhang
January-December 2015, 6(1):2-2
The Arabidopsis genome encodes numerous iron-containing proteins such as iron-sulfur (Fe-S) cluster proteins and hemoproteins. These proteins generally utilize iron as a cofactor, and they perform critical roles in photosynthesis, genome stability, electron transfer, and oxidation-reduction reactions. Plants have evolved sophisticated mechanisms to maintain iron homeostasis for the assembly of functional iron-containing proteins, thereby ensuring genome stability, cell development, and plant growth. Over the past few years, our understanding of iron-containing proteins and their functions involved in genome stability has expanded enormously. In this review, I provide the current perspectives on iron homeostasis in Arabidopsis, followed by a summary of iron-containing protein functions involved in genome stability maintenance and a discussion of their possible molecular mechanisms.
  7,624 478 8
A child with partial trisomy 4 (q26 – qterminal) resulting from paternally inherited translocation (4:18) associated with multiple congenital anomalies and death
Abhik Chakraborty, Santosh Kumar Panda, Nirmal Kumar Mohakud, Debarshi Roy, Swatishree Padhi, Shu Wen Koh, Manoor Prakash Hande, Birendranath Banerjee
January-December 2019, 10(1):1-1
DOI:10.4103/genint.genint_4_18  PMID:31160964
Parental balanced reciprocal translocations can result in partial aneuploidy in the offspring due to unbalanced meiotic segregation during gametogenesis. Herein, we report the phenotypic and cytogenetic characterization in a 9-day-old male child with partial trisomy of chromosome 4. Karyotyping of the proband and parents was performed along with multicolor fluorescence in situ hybridization (mFISH) of paternal chromosomes. Conventional cytogenetic analysis by karyotyping showed 47,XY,der(18),t(4;18)(q26;q22),+4 in proband, and the paternal karyotype was found as 47,XY,der(18),t(4;18)(q26;q22). mFISH analysis on paternal chromosomal preparations confirmed both region and origin of the balanced translocation. In this study, karyotyping helped us to identify both numerical and structural anomalies in the proband, and mFISH helped us to confirm our cytogenetic findings. Therefore, cytogenetic screening of both partners is recommended before pregnancy to rule out or confirm the presence of any numerical or structural anomaly in one, both, or none of the partners.
  7,261 590 -
The frequency of lymphocytes containing dumbbell-shaped nuclei depends on ionizing radiation dose and correlates with appearance of chromosomal aberrations
Viacheslav Yu Kravtsov, Alexandra A Livanova, Oleg V Belyakov, Regina F Fedortseva
January-December 2018, 9(1):1-7
DOI:10.4103/genint.genint_1_18  PMID:30820312
Nuclear anomalies of different types appear in cells in response to the action of ionizing radiation after the passage of the first mitotic division. In this article, we present the results of the study of the frequency of occurrence of three types of nuclear anomalies (“tailed” nuclei, nucleoplasmic bridges, and dumbbell-shaped nuclei) in vitro in human lymphocytes cultured with cytochalasin B when exposed to X-rays at doses of 0.0, 0.1, 0.2, 0.4, 0.5, 0.7, 1.0, 1.5, and 2.0 Gy. To stop the cell cycle of cultured lymphocytes after the first mitotic division, a cytokinesis block was performed using cytochalasin B. Dose-dependent curves of the occurrence of lymphocytes containing “tailed” nuclei, nucleoplasmic bridges, or dumbbell-shaped nuclei after irradiation have been constructed. At the same time, frequencies of occurrence of chromosomal aberrations (dicentric and ring chromosomes) in the culture of lymphocytes exposed to the same radiation doses were studied. Comparison of the frequencies of occurrence of dicentric and ring chromosomes with frequencies of occurrence of nuclear anomalies allows us to conclude that these nuclear anomalies are formed as a result of chromosomal aberrations arising in lymphocytes under the action of ionizing radiation. More than that, most of the chromosomal aberrations are converted into dumbbell-shaped nuclei in vitro in the culture of lymphocytes in the cytochalasin block.
  7,217 605 2
The application of imaging flow cytometry to high-throughput biodosimetry
Ruth C Wilkins, Matthew A Rodrigues, Lindsay A Beaton-Green
January-December 2017, 8(1):7-7
DOI:10.4103/2041-9414.198912  PMID:28250914
Biodosimetry methods, including the dicentric chromosome assay, the cytokinesis.block micronucleus assay and the γH2AX marker of DNA damage are used to determine the dose of ionizing radiation. These techniques are particularly useful when physical dosimetry is absent or questioned. While these assays can be very sensitive and specific, the standard methods need to be adapted to increase sample throughput in the case of a large.scale radiological/nuclear event. Recent modifications to the microscope.based assays have resulted in some increased throughput, and a number of biodosimetry networks have been, and continue to be, established and strengthened. As the imaging flow cytometer.(IFC) is a technology that can automatically image and analyze processed blood samples for markers of radiation damage, the microscope.based biodosimetry techniques can be modified for the IFC for high.throughput biological dosimetry. Furthermore, the analysis templates can be easily shared between networked biodosimetry laboratories for increased capacity and improved standardization. This review describes recent advances in IFC methodology and their application to biodosimetry.
  6,993 712 18
Biomarkers of ionizing radiation exposure: A multiparametric approach
Dimphy Zeegers, Shriram Venkatesan, Shu Wen Koh, Grace Kah Mun Low, Pallavee Srivastava, Neisha Sundaram, Swaminathan Sethu, Birendranath Banerjee, Manikandan Jayapal, Oleg Belyakov, Rajamanickam Baskar, Adayabalam S Balajee, M Prakash Hande
January-December 2017, 8(1):6-6
DOI:10.4103/2041-9414.198911  PMID:28250913
Humans are exposed to ionizing radiation not only through background radiation but also through the ubiquitous presence of devices and sources that generate radiation. With the expanded use of radiation in day.to.day life, the chances of accidents or misuse only increase. Therefore, a thorough understanding of the dynamic effects of radiation exposure on biological entities is necessary. The biological effects of radiation exposure on human cells depend on much variability such as level of exposure, dose rate, and the physiological state of the cells. During potential scenarios of a large.scale radiological event which results in mass casualties, dose estimates are essential to assign medical attention according to individual needs. Many attempts have been made to identify biomarkers which can be used for high throughput biodosimetry screening. In this study, we compare the results of different biodosimetry methods on the same irradiated cells to assess the suitability of current biomarkers and push forward the idea of employing a multiparametric approach to achieve an accurate dose and risk estimation.
  6,295 618 30
Identification and preliminary validation of radiation response protein(s) in human blood for a high-throughput molecular biodosimetry technology for the future
Saibadaiahun Nongrum, S Thangminlal Vaiphei, Joshua Keppen, Mandahakani Ksoo, Ettrika Kashyap, Rajesh N Sharan
January-December 2017, 8(1):5-5
DOI:10.4103/2041-9414.198910  PMID:28250912
The absence of a rapid and high-throughput technology for radiation biodosimetry has been a great obstacle in our full preparedness to cope with large-scale radiological incidents. The existing cytogenetic technologies have limitations, primarily due to their time-consuming methodologies, which include a tissue culture step, and the time required for scoring. This has seriously undermined its application in a mass casualty scenario under radiological emergencies for timely triage and medical interventions. Recent advances in genomics and proteomics in the postgenomic era have opened up new platforms and avenues to discover molecular biomarkers for biodosimetry in the future. Using a genomic-to-proteomic approach, we have identified a basket of twenty “candidate” radiation response genes.(RRGs) using DNA microarray and tools of bioinformatics immediately after ex vivo irradiation of freshly drawn whole blood of consenting and healthy human volunteers. The candidate RRGs have partially been validated using real-time quantitative polymerase chain reaction.(RT-qPCR or qPCR) to identify potential “candidate” RRGs at mRNA level. Two potential RRGs, CDNK1A and ZNF440, have so far been identified as genes with potentials to form radiation response proteins in liquid biopsy of blood, which shall eventually form the basis of fluorescence- or ELISA-based quantitative immunoprobe assay for a high-throughput technology of molecular biodosimetry in the future. More work is continuing.
  6,226 589 6
Exceptional association between Klinefelter syndrome and growth hormone deficiency
Sana Doubi, Zoubida Amrani, Hanan El Ouahabi, Saïd Boujraf, Farida Ajdi
January-December 2015, 6(1):3-3
Klinefelter syndrome (KS) is characterized in adults by the combination of a tall stature, small testes, gynecomastia, and azoospermia. This case is described in a North African population of the Mediterranean region of North Africa. We report the case of a male 16 years old, of Arab ethnic origin, and diagnosed with this syndrome, who had a small height in relation to a growth hormone (GH) deficiency and a history of absence seizures (generalized myoclonic epilepsy). The patient's size was <−2.8 standard deviation (SD) with weight <−3 SD. GH deficiency was isolated and confirmed by two dynamic tests (insulin - hypoglycemia tolerance test and clonidine) with normal hypothalamic magnetic resonance imaging (MRI). GH supplementation using recombinant GH was advocated, while gonadotropin treatment was deferred. Small size in children or adolescents should not eliminate the diagnosis of Klinefelter syndrome - on the contrary, the presence of any associated sign (brain maturation, delay in puberty, aggressiveness) should encourage one to request a karyotype for the diagnosis and appropriate care of any case of KS that can be associated with GH deficiency, or which is in a variant form (isochromosome Xq, 49,XXXXY).
  6,258 453 3
Conventional risk factors, telomere length, and ischemic heart disease: Insights into the mediation analysis
Shobhit Piplani, Madhav Prabhu, Nadezdha Niyarah Alemao, C Akash, Pradhum Ram, Sameer Ambar, Vijay Kumbar, Yashasvi Chugh, Siba P Raychauduri, Sanjay Kumar Chugh
January-December 2021, 12(1):1-7
Telomere length is regarded as a potential biomarker of biological ageing and is associated with various age-related diseases, such as ischemic heart disease (IHD), myocardial infarction, peripheral vascular disease, and cancer. As there is a paucity of study that deals with this influence, this study aimed to assess how the cardiovascular risk factors influence the risk of IHD by performing mediation analysis. A total of 407 males were included in the study. IHD was diagnosed through echocardiography and coronary angiography by determining the number of coronary vessels involved. Demographic data, clinical history, and laboratory investigations such as random blood sugar (RBS), fasting lipid profile, serum creatinine, and serum urea levels of all the subjects were measured and recorded. Serum uric acid and blood urea nitrogen (BUN) levels were significantly higher in IHD subjects compared to non-IHD subjects (P < 0.05). Body mass index (BMI), glycosylated hemoglobin (HbA1c), RBS, serum uric acid, serum creatinine, BUN, total cholesterol, triglycerides, and telomere length significantly differed between subjects with and without IHD (P < 0.05). Further, telomere length (P < 0.001), BMI (P < 0.001), and total cholesterol level (P < 0.001) were risk factors that significantly affected the incidence of IHD, as proved by logistic regression. It indicates that shorter telomeres contribute to increased risk of IHD, influenced by BMI, HbA1c, BUN, total cholesterol levels, and RBS (P < 0.001). The study established a link between telomere shortening, conventional risk factors, and IHD; moreover, the study takes care in the role of mediation analysis which is a novel idea as little is done in this area of biostatistics with telomere length. Overall, this further establishes that telomeres length might serve as the promising biomarkers in predicting the risk of IHD.
  5,930 446 2
Retrospective biological dosimetry at low and high doses of radiation and radioiodine impact on individual susceptibility to ionizing radiation
Antonina Cebulska-Wasilewska, Mateusz Krzysiek, Grażyna Krajewska, Artur Stępień, Paweł Krajewski
January-December 2017, 8(1):2-2
DOI:10.4103/2041-9414.198906  PMID:28250909
Iodine-131 (I-131) is often used in thyroid diagnostics and therapy. External and internal exposure to radioiodine can lead to molecular and cellular damage in peripheral blood lymphocytes. The aim of this study was to explore the influence of low and high doses of I-131 on susceptibility to ionizing radiation. Study groups consisted of 30 individuals free of thyroid diseases, 41 patients exposed diagnostically to low doses of I-131, and 37 hyperthyroidism patients exposed therapeutically to high doses. The standardized DNA repair competence assay was used to test the efficacy of the fast DNA repair process in G0 cells. Cytogenetic preparations were made in fresh blood samples before and after challenging cells in vitro with X-ray dose. The frequency of sister chromatid exchanges (SCE) and percentage of cells with significantly elevated numbers of SCE were used as cytogenetic biomarkers associated to homologous recombination and compared to reported earlier cytogenetic biomarkers of cancer risk. Strong individual variation in the biomarkers is observed in all investigated groups before and after challenging. Nevertheless, the efficiency of post challenging fast repair is significantly high in the patients exposed to diagnostic I-131 doses than in unexposed control group and linked to decreased cytogenetic damage. However, 5 weeks after administration of therapeutic doses, significant increases of unrepaired post challenging DNA and cytogenetic damages were observed indicating a health risk. Results also suggest that the appearance of cancers in immediate families might influence DNA repair differently in patients exposed to low than to high doses.
  5,839 476 5
Calibration curve for dicentric chromosomes induced in human blood lymphocytes exposed to gamma rays at a dose rate of 12.5 mgy/s
Tran Que, Pham Ngoc Duy, Bui Thi Kim Luyen
January-December 2016, 7(1):2-2
DOI:10.4103/2041-9414.197171  PMID:28217278
To develop a calibration curve for induction of dicentric chromosomes by radiation, we have used a 60Co gamma-ray source with dose rate of 12.5 mGy/s. Whole blood from 15 healthy donors was collected. Whole blood from each donor was divided equally into 8 parts for exposing to supposedly physical doses 0, 0.30, 0.50, 1.00, 1.50, 2.00, 3.00 and 4.00 Gy for a independent calibration curve. Whole blood from 15 donors was used to calibrate dose – effect and statistical for general calibration curve. Using Poisson test (U-test) for the distribution of dicentric chromosomes in the metaphases to determine the uniformity of the radiation field. The average from 15 independent calibration curves of linear correlated coefficient was determined to be r (y, d) = 0.5136 ± 0.0038. The model equation derived is y = aD + bD2 + C. The calibration equation of dose-effect was y = 1.01D + 4.43D2 + 0.56.
  5,832 442 1
Effects of valproic acid on radiation-induced chromosomal aberrations in human lymphocytes
Maria Vittoria Di Tomaso, Eric Gregoire, Wilner Martínez-López
January-December 2017, 8(1):4-4
DOI:10.4103/2041-9414.198909  PMID:28250911
One of the most widely employed histone deacetylases inhibitors in the clinic is the valproic acid (VA), proving to have a good tolerance and low side effects on human health. VA induces changes in chromatin structure making DNA more susceptible to damage induction and influence DNA repair efficiency. VA is also proposed as a radiosensitizing agent. To know if VA is suitable to sensitize human lymphocytes γ-irradiation in vitro, different types of chromosomal aberrations in the lymphocytes, either in the absence or presence of VA, were analyzed. For this purpose, blood samples from four healthy donors were exposed to γ-rays at a dose of 1.5 Gy and then treated with two different doses of VA (0.35 or 0.70 mM). Unstable and stable chromosomal aberrations were analyzed by means of fluorescence in situ hybridization. Human lymphocytes treated with VA alone did not show any increase in the frequency of chromosomal aberrations. However, a moderate degree of sensitization was observed, through the increase of chromosomal aberrations, when 0.35 mM VA was employed after γ-irradiation, whereas 0.70 mM VA did not modify chromosomal aberration frequencies. The lower number of chromosomal aberrations obtained when VA was employed at higher dose after γ-irradiation, could be related to the induction of a cell cycle arrest, a fact that should be taken into consideration when VA is employed in combination with physical or chemical agents.
  5,522 479 2
Towards establishing capacity for biological dosimetry at ghana atomic energy commission
Daniel Gyingiri Achel, Elom Achoribo, Sandra Agbenyegah, Rudolph M Adaboro, Shadrack Donkor, Nana A K Adu-Bobi, Akwasi A Agyekum, Felicia Akuamoa, Samuel N Tagoe, Kofi A Kyei, Joel Yarney, Antonio Serafin, John M Akudugu
January-December 2016, 7(1):3-3
DOI:10.4103/2041-9414.197173  PMID:28217279
The aim of this study was not only to obtain basic technical prerequisites for the establishment of capacity of biological dosimetry at the Ghana Atomic Energy Commission (GAEC) but also to stimulate interest in biological dosimetry research in Ghana and Sub-Saharan Africa. Peripheral blood from four healthy donors was exposed to different doses (0–6 Gy) of gamma rays from a radiotherapy machine and lymphocytes were subsequently stimulated, cultured, and processed according to standard protocols for 48–50 h. Processed cells were analyzed for the frequencies of dicentric and centric ring chromosomes. Radiation dose delivered to the experimental model was verified using GafChromic® EBT films in parallel experiments. Basic technical prerequisites for the establishment of capacity of biological dosimetry in the GAEC have been realized and expertise in the dicentric chromosome assay consolidated. We successfully obtained preliminary cytogenetic data for a dose-response relationship of the irradiated blood lymphocytes. The data strongly indicate the existence of significant linear (α) and quadratic (β) components and are consistent with those published for the production of chromosome aberrations in comparable absorbed dose ranges.
  5,497 378 1
Micronucleus assay-based evaluation of radiosensitivity of lymphocytes among inhabitants living in high background radiation area of Mamuju, West Sulawesi, Indonesia
Mukh Syaifudin, Vira Putri Defiyandra, Siti Nurhayati, Sofiati Purnami, Eko Pudjadi
January-December 2018, 9(1):2-2
DOI:10.4103/genint.genint_2_18  PMID:30820313
Naturally occurring radiation can be found all around us and account for most of the radiation received by human beings each year. Indonesia has a region with high-dose natural radiation located in the suburb of West Sulawesi province with a dose rate up to 2800 nSv/h; however, its impact was not fully understood. The aim of this study was to evaluate the radiosensitivity of 12 peripheral blood lymphocytes of inhabitant from high background radiation area (HBRA) and 10 from normal background radiation area (NBRA) based on cytokinesis-block micronucleus (CBMN) assay after challenged with 1.5 Gy of gamma ray. The analysis of CBMN was done according to standard procedure as per IAEA guidelines, and frequency of binucleate (mitotic) cells with micronuclei (MN) was scored in around 2000 binucleate lymphocytes cells per culture in microscopic analysis. Mean MN frequency for HBRA was lower than that of NBRA (0.121 vs. 0.189) after irradiation, indicating an adaptive response in HBRA group that resulted in less radiosensitivity; however, there was no statistically significant different (P > 0.05) between these two groups. The MN number was higher in women compared to men for both HBRA (0.15 vs. 0.09) and NBRA (0.216 vs. 0.147) groups. Besides, there was no statistically significant difference (P > 0.05) in Nuclear Division Index (NDI), as measured in 500 metaphase cells with published formula, between HBRA and NBRA samples (1.24 vs. 1.21). The lower MN frequency prompts us to conclude that there is an adaptive response in the lymphocytes of inhabitants as an indicator of lower radiosensitivity to the high natural radiation exposure. Further studies using large number of samples are required to obtain more comprehensive conclusion along with the assessment of other types of radiosensitivity-related biomarkers.
  5,415 446 2
Analysis of Xq27.3 fragility using the micronucleus-fluorescence In situ hybridization assay
Leyla Ozer, Hatice Ilgin Ruhi, Isik Bökesoy
2020, 11(1):1-1
Chromosome fragile sites tend to form gap or break in chromosomes following when the cell exposed to replication stress. Folic acid deprivation in the culture medium induces folate-sensitive rare fragile sites, such as FRAXA which is responsible for the fragile X mental retardation syndrome. Chromosome instability at fragile sites can be evaluated by biomarkers of genomic instability such as frequency of micronuclei (MN). It was aimed to analyse the chromosome content of MN in Fragile X cells during folate deprivation by the MN-fluorescence in situ hybridization (FISH) method. Samples from five Fragile X syndrome patients, diagnosed using cytogenetic and molecular methods, as well as from their parents and five controls were included in the study. Blood samples were cultured in two different culture media (folate-deficient and normal). Results of MN-FISH test were analysed in terms of MN frequency and chromosome content of MN. An accumulation of MN in Fragile X patients, mainly containing T (+) or C (+) MN or T (+) plus C (+) MN in binucleated cells was found. Finally, MN-FISH analysis allowed confirming that the increase in MN frequency is due to a higher sensitivity to chromosome breakage along the X chromosome.
  5,465 326 1
Radiation-induced Chromosome Instability: The role of dose and dose rate
Eman Mohammed Elbakrawy, Mark A Hill, Munira A Kadhim
January-December 2019, 10(1):3-3
Nontargeted effects include radiation-induced genomic instability (RIGI) which is observed in the progeny of cells exposed to ionizing radiation and can be manifested in different ways, including chromosomal instability and micronucleus (MN) formation. Since genomic instability is commonly observed in tumors and has a role in tumor progression, RIGI has the potential of being an important mechanism for radiation-induced cancer. The work presented explores the role of dose and dose rate on RIGI, determined using a MN assay, in normal primary human fibroblast (HF19) cells exposed to either 0.1 Gy or 1 Gy of X-rays delivered either as an acute (0.42 Gy/min) or protracted (0.0031 Gy/min) exposure. While the expected increase in MN was observed following the first mitosis of the irradiated cells compared to unirradiated controls, the results also demonstrate a significant increase in MN yields in the progeny of these cells at 10 and 20 population doublings following irradiation. Minimal difference was observed between the two doses used (0.1 and 1 Gy) and the dose rates (acute and protracted). Therefore, these nontargeted effects have the potential to be important for the low-dose and dose-rate exposure. The results also show an enhancement of the cellular levels of reactive oxygen species after 20 population doublings, which suggests that ionising radiation (IR) could potentially perturb the homeostasis of oxidative stress and so modify the background rate of endogenous DNA damage induction. In conclusion, the investigations have demonstrated that normal primary human fibroblast (HF19) cells are susceptible to the induction of early DNA damage and RIGI, not only after a high dose and high dose rate exposure to low linear energy transfer, but also following low dose, low dose rate exposures. The results suggest that the mechanism of radiation induced RIGI in HF19 cells can be correlated with the induction of reactive oxygen species levels following exposure to 0.1 and 1 Gy low-dose rate and high-dose rate x-ray irradiation.
  5,257 462 -
Intercomparison in cytogenetic dosimetry among 22 laboratories in China
Jian Xiang Liu, Yan Pan, Jian Lei Ruan, Chunnan Piao, Xu Su
January-December 2016, 7(1):6-6
DOI:10.4103/2041-9414.197164  PMID:28217282
As part of a regional International Atomic Energy Agency-coordinated research project with the support from the National Health and Family Planning Commission of China, 22 laboratories participated in the intercomparison in cytogenetic dosimetry in China. Slides for chromosomal aberrations were prepared by the Department of Radiation Epidemiology, National Institute for Radiological Protection, which organized the exercise. Slides were sent to the other participating laboratories through Express Mail Service. For estimates of dose, each laboratory scored the frequency of dicentrics plus centric rings chromosomes. The whole blood samples were irradiated with 60Co γ-rays (1.3 Gy, 2.4 Gy and 1.5 Gy, 2.6 Gy). Each laboratory got one group of the slides. Ten of the 44 estimates of dose fell within ±5% of the true physical dose, 12 fell within ±5–10%, 9 fell within ±10–15%, 12 fell within ±15–20%, while only one sample fell ± >20%. The evaluation of the respective dose was achieved by 21 laboratories.
  5,267 392 2
Optimizing the microscopy time schedule for chromosomal dosimetry of high-dose and partial-body irradiations
Volodymyr A Vinnikov
January-December 2017, 8(1):3-3
DOI:10.4103/2041-9414.198908  PMID:28250910
The methodology of cytogenetic triage can be improved by optimizing a schedule of microscopy for different exposure scenarios. Chromosome aberrations were quantified by microscopy in human blood lymphocytes irradiated in vitro to ~2, 4, and 12 Gy acute 60Co γ-rays mixed with the unirradiated blood simulating 10%, 50%, 90%, and 100% exposure and in along with a sample from a homogeneous exposure to ~20 Gy. Biodosimetry workload was statistically modeled assuming that 0.5, 1, 5, or 25 h was available for scoring one case or for analysis of up to 1000 cells or 100 dicentrics plus centric rings by one operator. A strong negative correlation was established between the rates of aberration acquisition and cell recording. Calculations showed that the workload of 1 case per operator per·day (5 h of scoring by microscopy) allows dose estimates with high accuracy for either 90%–100% irradiations of 2 Gy or 50%–90% irradiations of 4–12 Gy; lethal homogeneous (100%) exposures of 12 and 20 Gy can be evaluated with just 1 h of microscopy. Triage analysis of 0.5 h scoring per case results in the minimum tolerable accuracy only for partial. and total.body exposure of 4–20 Gy. Time.related efficacy of conventional biodosimetry depends primarily on the aberration yield in the sample, which is dependent on the radiation dose and its distribution in the patient's body. An optimized schedule of microscopy scoring should be developed for different exposure scenarios in each laboratory to increase their preparedness to radiological emergencies.
  5,134 411 3
Strengthening biological dosimetry in member states of the international atomic energy agency
Prakash Hande, Rajesh Sharan, Oleg Belyakov
January-December 2016, 7(1):1-1
DOI:10.4103/2041-9414.197170  PMID:28217277
  5,067 459 1
Study on γH2AX expression of lymphocytes as a biomarker in radiation biodosimetry
Yan Pan, Gang Gao, Jian Lei Ruan, Jian Xiang Liu
January-December 2016, 7(1):10-10
DOI:10.4103/2041-9414.197167  PMID:28217286
Flow cytometry analysis was used to detect the changes of γH2AX protein expression in human peripheral blood lymphocytes. In the dose-effect study, the expression of γH2AX was detected 1 h after irradiation with 60Co γ-rays at doses of 0, 0.5, 1, 2, 4, and 6 Gy. Blood was cultivated for 0, 1, 2, 4, 6, 12, and 24 h after 4 Gy 60Co γ-rays irradiation for the time-effect study. At the same time, the blood was divided into four treatment groups (ultraviolet [UV] irradiation, 60Co γ-rays irradiation, UV plus 60Co γ-rays irradiation, and control group) to detect the changes of protein expression of γH2AX. The results showed that the γH2AX protein expression was in dose-effect and time-effect relationship with 60Co γ-rays. The peak expression of γH2AX was at 1 h after 60Co γ-ray irradiation and began to decrease quickly. Compared to irradiation with 60Co γ-rays alone, the expression of γH2AX was not significantly changed after irradiation with 60Co γ-rays plus UV. Dose rate did not significantly change the expression of γH2AX. The expression of γH2AX induced by 60Co γ-rays was basically consistent with the mice in vivo and in vitro. The results revealed that the detection of γH2AX protein expression changes in peripheral blood lymphocyte by flow cytometry analysis is reasonable and may be useful for biodosimetry.
  5,055 451 3
Biodosimetry of persons chronically exposed to low and therapeutic doses of ionizing radiation
Alla Zedginidze, Ema Namchevadze, George Ormocadze, Archil Kapanadze, Tamara Nikuradze, Darejan Lomidze
January-December 2016, 7(1):12-12
DOI:10.4103/2041-9414.197169  PMID:28217288
Dynamic changes of the chromosomal aberrations and the DNA damage were analyzed in individuals exposed to low and therapeutic doses of radiation. The investigation included 37 persons living in areas where the radioactive sources were discovered 10–12 years ago. It was established by biodosimetry methods that the examined persons had absorbed dose of 0.2–0.7 Gy or had increased number of chromosomal aberrations, though insufficient to determine a dose. Clinical examination, chromosomal analysis, and assay of DNA damage by the comet (single-cell gel electrophoresis) assay were carried out. There was no correlation between the doses received 10 years ago and the cytogenetic changes with clinical outcome. The effect of the local fractionated gamma-irradiation with doses of 40–70 Gy was studied in cancer patients with localized head and neck tumors. The study of chromosomal abnormalities, the DNA damages by the comet assay, and the micronuclei detection of the buccal cells revealed a statistically significant correlation between the initial cytogenetic indices in cancer patients and their dynamic changes during and after the radiation exposure. In addition, the correlation was detected between the initial cytogenetic parameters and the functional stage of red blood system. Our results allow us to conclude that there is a need for further research to estimate the individual radiation risk to optimize and individualize the subsequent medical management of radiotherapy.
  5,084 420 4
Construction of calibration curve for premature chromosome condensation assay for dose assessment
Elizaveta G Neronova
January-December 2016, 7(1):9-9
DOI:10.4103/2041-9414.197166  PMID:28217285
Cytogenetic dosimetry plays an important role in the triage and medical management of affected people in radiological incidents/accidents. Cytogenetic biodosimetry uses different methods to estimate the absorbed dose in the exposed individuals, and each approach has its advantages and disadvantages. Premature chromosome condensation (PCC) assay presents several advantages that hopefully fulfill the gaps identified in the other cytogenetic methods. To introduce this technique into the panel of other cytogenetic methods, a calibration curve for PCC after γ-irradiation was generated for our laboratory.
  5,040 402 5
Establishment of a dose-response curve for X-ray-induced micronuclei in human lymphocytes
Yanti Lusiyanti, Zubaidah Alatas, Mukh Syaifudin, Sofiati Purnami
January-December 2016, 7(1):7-7
DOI:10.4103/2041-9414.197162  PMID:28217283
The cytokinesis-block micronucleus assay in peripheral blood lymphocytes is an established technique for biodosimetry. The aim of this project was to generate a X-ray induced micronuclei (MN) curve for peripheral blood lymphocytes taken from five healthy donors. The blood samples were irradiated with X-rays of 122 KeV at a dose rate of 0.652 Gy/min to doses of 0.5, 1, 2, 3, and 4 Gy. The blood samples were then cultured for 72 h at 37°C and processed following the International Atomic Energy Agency standard procedure with slight modifications. The result showed that the yields of MN frequencies were increased with the increase of radiation dose. Reconstruction of the relationship of MN with dose was fitted to a linear-quadratic model using Chromosome Aberration Calculation Software version 2.0. Due to their advantages, mainly, the dependence on radiation dose and dose rate, despite their limitation, these curves will be useful as alternative method for in vitro dose reconstruction and can support the preparedness for public or occupational radiation overexposure and protection. The results reported here also give us confidence to apply the obtained calibration curve of MN for future biological dosimetry requirements in Indonesia.
  4,971 438 8
Assessment of correlation between chromosomal radiosensitivity of peripheral blood lymphocytes after In vitro irradiation and normal tissue side effects for cancer patients undergoing radiotherapy
Kamile Guogyte, Aista Plieskienė, Rima Ladygienė, Žygimantas Vaisiūnas, Olga Sevriukova, Vinsas Janušonis, Julius Žiliukas
January-December 2017, 8(1):1-1
DOI:10.4103/2041-9414.198907  PMID:28250908
Patients receiving identical radiation treatments experience different effects, from undetectable to severe, on normal tissues. A crucial factor of radiotherapy related side effects is individual radiosensitivity. It is difficult to spare surrounding normal tissues delivering radiation to cancer cells during radiotherapy. Therefore, it may be useful to develop a simple routine cytogenetic assay which would allow the screening of a large number of individuals for radiosensitivity optimizing tumor control rates and minimizing severe radiotherapy effects with possibility to predict risk level for developing more severe early normal tissue adverse events after irradiation. This study was conducted to assess the correlation between in vitro radiosensitivity of peripheral blood lymphocytes from cancer patients who are undergoing radiotherapy using the cytokinesis-block micronucleus (CBMN), G2 chromosomal radiosensitivity assays, and normal tissue acute side effects. The CBMN and G2 chromosomal radiosensitivity assays were performed on blood samples taken from cancer patients before radiotherapy, after first fractionation, and after radiotherapy. Acute normal tissue reactions were graded according to the Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer. This study suggests that there is a correlation between higher frequency of micronuclei after in vitro irradiation of blood samples and higher degree of normal tissue reactions. In addition, higher number of chromatid breaks was observed in patients with more severe normal tissue reactions. This pilot study included only 5 cancer patients, and therefore, further studies with a bigger cohort are required to identify radiosensitive patients.
  4,790 562 9