Volodymyr Vinnikov - Academia.edu (original) (raw)
Papers by Volodymyr Vinnikov
International journal of radiation biology, Apr 22, 2024
Ukraïnsʹkij radìologìčnij ta onkologìčnij žurnal, Mar 29, 2021
Огляд літератури 89 Literature review Ключові слова: індивідуальна радіочутливість, предиктори, п... more Огляд літератури 89 Literature review Ключові слова: індивідуальна радіочутливість, предиктори, променева терапія, променеві реакції в нормальних тканинах, клоногенна виживаність клітин, колонієутворення, апоптоз, контрольні точки клітинного циклу. Для цитування: Вінніков В. А., Рубльова Т. В. Предиктори променевих ускладнень у радіаційній онкології на основі тестів на виживаність клітин після ex vivo опромінення: огляд літератури.
PubMed, Feb 18, 2005
The post-irradiation changes of dicentric and centric ring levels were studied in Chernobyl liqui... more The post-irradiation changes of dicentric and centric ring levels were studied in Chernobyl liquidators using the data of 507 individual chromosomal surveys of persons sampled at different time after their activities at Chernobyl NPP accident zone. The time-effect relationship within 0-10.5 years after exposure was displayed as exponential decline of the mean chromosome exchange frequency with average decay half-time 2.2 y. During 10.5-13 years after exposure the increasing and stabilization of chromosome exchange yield on the level 2-3-times higher than control was observed. In the first few months after irradiation the dicentric and centric ring frequency in liquidators had the clear reverse correlation with the duration of person's duties at the Chernobyl zone. The parameters of unstable chromosome exchange elimination were independent on the initially induced aberration yield, that resulted in earlier reaching the subcontrol level in persons who had more protracted duration of duties at the Chernobyl accident zone.
PubMed, Feb 4, 2006
The paper presents the results of the cohortal biodosimetry carried out in 435 Chernobyl clean-up... more The paper presents the results of the cohortal biodosimetry carried out in 435 Chernobyl clean-up workers, who were surveyed with the conventional cytogenetic technique in terms from several days to 10 years after the end of their duties in the Chernobyl accident exclusive zone. An empirical model of the aberrant cell dynamics was utilized for the calculation of mean initial yields of dicentrics and centric rings in groups with different terms and duration of staying in the Chernobyl zone. Corresponding protracted irradiation doses estimated from aberration levels ranged from 79 to 670 mGy. The probabilistic distribution of the radiation doses was constructed by the applying the Bayesian analysis to initial individual chromosome exchange yields extrapolated to the exposure termination moment. This distribution was characterized by the mean dose about 460 mGy and maximum of probability density in the interval of 50-300 mGy. For the late somatic risk assessment in clean-up workers the probabilistic distribution of equivalentally-acute radiation doses was proposed; that had the mean value about 270 mGy, modal classes of 250-350 mGy and 99.8% of the probability density concentrated within the dose range from 0 to 1000 mGy.
Radiatsionnaia biologiia, radioecologiia / Rossiĭskaia akademiia nauk
Eighteen Ukrainian evacuees from the Chernobyl exclusive zone, twenty one inhabitants of radioact... more Eighteen Ukrainian evacuees from the Chernobyl exclusive zone, twenty one inhabitants of radioactively contaminated areas of Belarus and twelve control donors age-matched to the exposed persons were investigated 14-15 years after the Chernobyl accident for chromosomal aberration yields detected in blood lymphocytes by fluorescence in situ hybridisation technique. Unstable aberration yields measured in both Chernobyl cohorts were close to the background frequencies. Positive age-dependence trends in control donors were determined for the all type stable aberration levels. In evacuees the tendency for diminishing the difference between them and controls for stable aberration levels with persons' age increasing was found. The total stable chromosome exchange yields in evacuees 46-55 years old and inhabitants of areas with low contamination level didn't exceed the control values, but for younger evacuees and inhabitants of sufficiently contaminated regions the statistical increa...
T͡Sitologii͡a i genetika
Dynamics of cytogenetic anomalies in liquidators of the Chernobyl accident has been studied. Dice... more Dynamics of cytogenetic anomalies in liquidators of the Chernobyl accident has been studied. Dicentric and ring frequencies appeared to be the most informative criteria of radio-induced chromosome aberrations. The rate of cell elimination with dicentrics and rings was higher in liquidators exposed to more than 25 cGy of radiation that in those exposed to less than 25 cGy of radiation. The rate of elimination of chromatid-type aberrations and genomic mutations was very low in the group of liquidators exposed to higher dose of radiation.
Cancers
External beam radiation therapy leads to cellular activation of the DNA damage response (DDR). DN... more External beam radiation therapy leads to cellular activation of the DNA damage response (DDR). DNA double-strand breaks (DSBs) activate the ATM/CHEK2/p53 pathway, inducing the transcription of stress genes. The dynamic nature of this transcriptional response has not been directly observed in vivo in humans. In this study we monitored the messenger RNA transcript abundances of nine DNA damage-responsive genes (CDKN1A, GADD45, CCNG1, FDXR, DDB2, MDM2, PHPT1, SESN1, and PUMA), eight of them regulated by p53 in circulating blood leukocytes at different time points (2, 6–8, 16–18, and 24 h) in cancer patients (lung, neck, brain, and pelvis) undergoing radiotherapy. We discovered that, although the calculated mean physical dose to the blood was very low (0.038–0.169 Gy), an upregulation of Ferredoxin reductase (FDXR) gene transcription was detectable 2 h after exposure and was dose dependent from the lowest irradiated percentage of the body (3.5% whole brain) to the highest, (up to 19.4%,...
Radiatsionnaia biologiia, radioecologiia / Rossiĭskaia akademiia nauk
The cytogenetic screening was carried out in 100 Chernobyl clean-up workers (liquidators) with re... more The cytogenetic screening was carried out in 100 Chernobyl clean-up workers (liquidators) with registered doses during 1 year after exposure. The bayesian analysis has been applied for constructing the individual distribution of probability density for biological doses estimated from dicentric and centric ring yields in liquidators. The coincidence of the biological and registered dose has been found in 25% of cases; among the rest persons the documented doses exceeded the biological estimations in 25% of cases and the cytogenetic doses were higher than registered ones in 50% of cases. The total distribution of biological doses was constructed by pooling the individual data in 50 mGy dose intervals. The distribution obtained had the maximum at 300-350 mGy and contained 68% of probability density in the dose range 0-1000 mGy. The probabilistic approach in cohort biodosimetry showed the necessity of corrections in radiogenic risk assessment for Chernobyl liquidators. The advantages of...
Seminars in nuclear medicine, 2021
Radiation dosimetric biomarkers have found applications beyond radiation protection area and now ... more Radiation dosimetric biomarkers have found applications beyond radiation protection area and now are actively introduced into clinical practice. Cytogenetic assays appeared to be a valuable tool for individualized quantifying radiation effects in patients, with high capability for assessing genotoxicity of various medical exposure modalities and providing meaningful radiation dose estimates for prognoses of radiation-related cancer risk. This review summarized current data on the use of biological dosimetry methods in patients undergoing various medical irradiations to low doses. The highlighted topics include basic aspects of biological dosimetry and its limitations in the range of low radiation doses, and main patterns of in vivo induction of radiation biomarkers in clinical exposure scenarios, occurring in X-ray diagnostics, computed tomography, interventional radiology, low dose radiotherapy, and nuclear medicine (internally administered 131I and other radiopharmaceuticals). Add...
International journal of radiation biology, 2021
BACKGROUND A detonation of nuclear weapon (NW) is considered as one of the most devastating radio... more BACKGROUND A detonation of nuclear weapon (NW) is considered as one of the most devastating radiological scenarios in the list of modern global threats. An essential proportion of victims in a mass casualty radiation event may require an immediate medical care due to radiation combined injuries (RCI). Surprisingly, there is a lack of clear guidance for quantitative prognosis of the spatial distribution of expected RCI casesin a given nuclear explosion scenario. PURPOSE This work is aimed at the presentation of a new, improved model, allowing more confident evaluation of the contributions from different NW destructive forces to RCI formation, thus leading to more accurate approximation of the zone around the epicentre for a guided search for RCI cases. MATERIALS AND METHODS The model is made compatible with a classic approach and provides the estimates of radial distance from the epicenter, at which NW explosion can produce RCI. Mathematical formalism comprises a set of equations for...
Radiation Protection Dosimetry, 1997
Lymphocytes from some evacuees from Prypiat and clean-up workers (liquidators) have been studied ... more Lymphocytes from some evacuees from Prypiat and clean-up workers (liquidators) have been studied for chromosomal aberrations. When dicentric yields from subjects are pooled in various ways, by date of evacuation, date of working at Chemobyl or delay in blood sampling, the resultant mean dose estimates are higher than have been generally assumed from dose reconstructions for Prypiat citizens or personal dosemeters worn by liquidators. Some of this difference may be due to the selection of subjects for study. However, dicentrics in one cohort of randomly selected evacuees, sampled very promptly, indicated a mean dose of ∼300 mGy which is significantly in excess of mean dose reconstructions of ∼10-20 mSv.
Genome Integrity
be performed successfully only if the aberration scoring has been done with sufficient accuracy. ... more be performed successfully only if the aberration scoring has been done with sufficient accuracy. [3] The optimization of uncertainties in dose estimates through defining the required numbers of metaphases scored and aberrations found has been effectively resolved for low-dose radiation exposures using an expertise mode (manual microscope scoring of 1000 cells per sample) of cytogenetic analysis [4] and to some extent for a wider dose range of homogeneous exposure. [5] However, with one exception, [3] no such attempt has been made for partial-body exposure scenarios. There are a growing number of reports regarding triage biodosimetry of partial-body exposures performed in experiments with in vitro simulations. [6-12] These studies focused mainly on the accuracy of dose estimates and their efficacy in classifying samples between triage categories. Much less information can be found in the literature regarding the speed of collecting the necessary number of metaphases or aberrations in scenarios of inhomogeneous exposure. Furthermore, many authors presented comparisons of the accuracy of manual and automated cytogenetic analysis, but only a few studies [8,13] showed
Dosimetric biomarkers have been effectively and intensively used for a long time in the area of r... more Dosimetric biomarkers have been effectively and intensively used for a long time in the area of radiation protection. In contrast to that, no robust standards or widely accepted protocols for application of these end-points in radiotherapy, diagnostic and interventional radiology and nuclear medicine exist to date. The International Atomic Energy Agency (IAEA) organized the review of the available data on the possibilities of the use of dosimetric biomarkers in medical irradiation scenarios. The resultant Technical Report also contains a summary of identified problems, gaps in knowledge, limitations in methodology and recommendations for their overcoming. This work provided a conceptual background for the initiation of a new IAEA Coordinated Research Project E35010, MEDBIODOSE (2017-21), which is aimed specifically at the development and improvement of applications of biodosimetric markers in clinical practice.
Journal of Personalized Medicine
A search for effective methods for the assessment of patients’ individual response to radiation i... more A search for effective methods for the assessment of patients’ individual response to radiation is one of the important tasks of clinical radiobiology. This review summarizes available data on the use of ex vivo cytogenetic markers, typically used for biodosimetry, for the prediction of individual clinical radiosensitivity (normal tissue toxicity, NTT) in cells of cancer patients undergoing therapeutic irradiation. In approximately 50% of the relevant reports, selected for the analysis in peer-reviewed international journals, the average ex vivo induced yield of these biodosimetric markers was higher in patients with severe reactions than in patients with a lower grade of NTT. Also, a significant correlation was sometimes found between the biodosimetric marker yield and the severity of acute or late NTT reactions at an individual level, but this observation was not unequivocally proven. A similar controversy of published results was found regarding the attempts to apply G2- and γH2A...
Applied Radiation and Isotopes
Scientific reports, Jan 12, 2018
Previous investigations in gene expression changes in blood after radiation exposure have highlig... more Previous investigations in gene expression changes in blood after radiation exposure have highlighted its potential to provide biomarkers of exposure. Here, FDXR transcriptional changes in blood were investigated in humans undergoing a range of external radiation exposure procedures covering several orders of magnitude (cardiac fluoroscopy, diagnostic computed tomography (CT)) and treatments (total body and local radiotherapy). Moreover, a method was developed to assess the dose to the blood using physical exposure parameters. FDXR expression was significantly up-regulated 24 hr after radiotherapy in most patients and continuously during the fractionated treatment. Significance was reached even after diagnostic CT 2 hours post-exposure. We further showed that no significant differences in expression were found between ex vivo and in vivo samples from the same patients. Moreover, potential confounding factors such as gender, infection status and anti-oxidants only affect moderately F...
Radiation Protection Dosimetry, Nov 25, 2013
Classical methods of assessing the uncertainty associated with radiation doses estimated using cy... more Classical methods of assessing the uncertainty associated with radiation doses estimated using cytogenetic techniques are now extremely well defined. However, several authors have suggested that a Bayesian approach to uncertainty estimation may be more suitable for cytogenetic data, which are inherently stochastic in nature. The Bayesian analysis framework focuses on identification of probability distributions (for yield of aberrations or estimated dose), which also means that uncertainty is an intrinsic part of the analysis, rather than an 'afterthought'. In this paper Bayesian, as well as some more advanced classical, data analysis methods for radiation cytogenetics are reviewed that have been proposed in the literature. A practical overview of Bayesian cytogenetic dose estimation is also presented, with worked examples from the literature.
Http Dx Doi Org 10 1667 Rr2228 1, Jul 14, 2010
The scientific literature concerning cytogenetic biodosimetry has been reviewed to identify the r... more The scientific literature concerning cytogenetic biodosimetry has been reviewed to identify the range of scenarios of radiation exposure where biodosimetry has been carried out. Limitations in the existing standardized statistical methodology have been identified and categorized, and the reasons for these limitations have been explored. Statistical problems generally occur due to either low numbers of aberrations leading to large uncertainties or deviations in aberration-per-cell distributions leading to over- or under-dispersion with respect to the Poisson model. A number of difficulties also stem from limitations of the classical statistical methodology, which requires that chromosome aberration yields be considered as something "fixed" and thus provides a deterministic estimate of radiation dose and associated confidence limits (because an assignment of a probability to an event is based solely on the observed frequency of occurrence of the event). Therefore, it is suggested that solutions to the listed problems should be based in the Bayesian framework. This will allow the investigator to take a probabilistic approach to analysis of cytogenetic data, which can be considered highly appropriate for biological dose estimation.
International journal of radiation biology, Apr 22, 2024
Ukraïnsʹkij radìologìčnij ta onkologìčnij žurnal, Mar 29, 2021
Огляд літератури 89 Literature review Ключові слова: індивідуальна радіочутливість, предиктори, п... more Огляд літератури 89 Literature review Ключові слова: індивідуальна радіочутливість, предиктори, променева терапія, променеві реакції в нормальних тканинах, клоногенна виживаність клітин, колонієутворення, апоптоз, контрольні точки клітинного циклу. Для цитування: Вінніков В. А., Рубльова Т. В. Предиктори променевих ускладнень у радіаційній онкології на основі тестів на виживаність клітин після ex vivo опромінення: огляд літератури.
PubMed, Feb 18, 2005
The post-irradiation changes of dicentric and centric ring levels were studied in Chernobyl liqui... more The post-irradiation changes of dicentric and centric ring levels were studied in Chernobyl liquidators using the data of 507 individual chromosomal surveys of persons sampled at different time after their activities at Chernobyl NPP accident zone. The time-effect relationship within 0-10.5 years after exposure was displayed as exponential decline of the mean chromosome exchange frequency with average decay half-time 2.2 y. During 10.5-13 years after exposure the increasing and stabilization of chromosome exchange yield on the level 2-3-times higher than control was observed. In the first few months after irradiation the dicentric and centric ring frequency in liquidators had the clear reverse correlation with the duration of person's duties at the Chernobyl zone. The parameters of unstable chromosome exchange elimination were independent on the initially induced aberration yield, that resulted in earlier reaching the subcontrol level in persons who had more protracted duration of duties at the Chernobyl accident zone.
PubMed, Feb 4, 2006
The paper presents the results of the cohortal biodosimetry carried out in 435 Chernobyl clean-up... more The paper presents the results of the cohortal biodosimetry carried out in 435 Chernobyl clean-up workers, who were surveyed with the conventional cytogenetic technique in terms from several days to 10 years after the end of their duties in the Chernobyl accident exclusive zone. An empirical model of the aberrant cell dynamics was utilized for the calculation of mean initial yields of dicentrics and centric rings in groups with different terms and duration of staying in the Chernobyl zone. Corresponding protracted irradiation doses estimated from aberration levels ranged from 79 to 670 mGy. The probabilistic distribution of the radiation doses was constructed by the applying the Bayesian analysis to initial individual chromosome exchange yields extrapolated to the exposure termination moment. This distribution was characterized by the mean dose about 460 mGy and maximum of probability density in the interval of 50-300 mGy. For the late somatic risk assessment in clean-up workers the probabilistic distribution of equivalentally-acute radiation doses was proposed; that had the mean value about 270 mGy, modal classes of 250-350 mGy and 99.8% of the probability density concentrated within the dose range from 0 to 1000 mGy.
Radiatsionnaia biologiia, radioecologiia / Rossiĭskaia akademiia nauk
Eighteen Ukrainian evacuees from the Chernobyl exclusive zone, twenty one inhabitants of radioact... more Eighteen Ukrainian evacuees from the Chernobyl exclusive zone, twenty one inhabitants of radioactively contaminated areas of Belarus and twelve control donors age-matched to the exposed persons were investigated 14-15 years after the Chernobyl accident for chromosomal aberration yields detected in blood lymphocytes by fluorescence in situ hybridisation technique. Unstable aberration yields measured in both Chernobyl cohorts were close to the background frequencies. Positive age-dependence trends in control donors were determined for the all type stable aberration levels. In evacuees the tendency for diminishing the difference between them and controls for stable aberration levels with persons' age increasing was found. The total stable chromosome exchange yields in evacuees 46-55 years old and inhabitants of areas with low contamination level didn't exceed the control values, but for younger evacuees and inhabitants of sufficiently contaminated regions the statistical increa...
T͡Sitologii͡a i genetika
Dynamics of cytogenetic anomalies in liquidators of the Chernobyl accident has been studied. Dice... more Dynamics of cytogenetic anomalies in liquidators of the Chernobyl accident has been studied. Dicentric and ring frequencies appeared to be the most informative criteria of radio-induced chromosome aberrations. The rate of cell elimination with dicentrics and rings was higher in liquidators exposed to more than 25 cGy of radiation that in those exposed to less than 25 cGy of radiation. The rate of elimination of chromatid-type aberrations and genomic mutations was very low in the group of liquidators exposed to higher dose of radiation.
Cancers
External beam radiation therapy leads to cellular activation of the DNA damage response (DDR). DN... more External beam radiation therapy leads to cellular activation of the DNA damage response (DDR). DNA double-strand breaks (DSBs) activate the ATM/CHEK2/p53 pathway, inducing the transcription of stress genes. The dynamic nature of this transcriptional response has not been directly observed in vivo in humans. In this study we monitored the messenger RNA transcript abundances of nine DNA damage-responsive genes (CDKN1A, GADD45, CCNG1, FDXR, DDB2, MDM2, PHPT1, SESN1, and PUMA), eight of them regulated by p53 in circulating blood leukocytes at different time points (2, 6–8, 16–18, and 24 h) in cancer patients (lung, neck, brain, and pelvis) undergoing radiotherapy. We discovered that, although the calculated mean physical dose to the blood was very low (0.038–0.169 Gy), an upregulation of Ferredoxin reductase (FDXR) gene transcription was detectable 2 h after exposure and was dose dependent from the lowest irradiated percentage of the body (3.5% whole brain) to the highest, (up to 19.4%,...
Radiatsionnaia biologiia, radioecologiia / Rossiĭskaia akademiia nauk
The cytogenetic screening was carried out in 100 Chernobyl clean-up workers (liquidators) with re... more The cytogenetic screening was carried out in 100 Chernobyl clean-up workers (liquidators) with registered doses during 1 year after exposure. The bayesian analysis has been applied for constructing the individual distribution of probability density for biological doses estimated from dicentric and centric ring yields in liquidators. The coincidence of the biological and registered dose has been found in 25% of cases; among the rest persons the documented doses exceeded the biological estimations in 25% of cases and the cytogenetic doses were higher than registered ones in 50% of cases. The total distribution of biological doses was constructed by pooling the individual data in 50 mGy dose intervals. The distribution obtained had the maximum at 300-350 mGy and contained 68% of probability density in the dose range 0-1000 mGy. The probabilistic approach in cohort biodosimetry showed the necessity of corrections in radiogenic risk assessment for Chernobyl liquidators. The advantages of...
Seminars in nuclear medicine, 2021
Radiation dosimetric biomarkers have found applications beyond radiation protection area and now ... more Radiation dosimetric biomarkers have found applications beyond radiation protection area and now are actively introduced into clinical practice. Cytogenetic assays appeared to be a valuable tool for individualized quantifying radiation effects in patients, with high capability for assessing genotoxicity of various medical exposure modalities and providing meaningful radiation dose estimates for prognoses of radiation-related cancer risk. This review summarized current data on the use of biological dosimetry methods in patients undergoing various medical irradiations to low doses. The highlighted topics include basic aspects of biological dosimetry and its limitations in the range of low radiation doses, and main patterns of in vivo induction of radiation biomarkers in clinical exposure scenarios, occurring in X-ray diagnostics, computed tomography, interventional radiology, low dose radiotherapy, and nuclear medicine (internally administered 131I and other radiopharmaceuticals). Add...
International journal of radiation biology, 2021
BACKGROUND A detonation of nuclear weapon (NW) is considered as one of the most devastating radio... more BACKGROUND A detonation of nuclear weapon (NW) is considered as one of the most devastating radiological scenarios in the list of modern global threats. An essential proportion of victims in a mass casualty radiation event may require an immediate medical care due to radiation combined injuries (RCI). Surprisingly, there is a lack of clear guidance for quantitative prognosis of the spatial distribution of expected RCI casesin a given nuclear explosion scenario. PURPOSE This work is aimed at the presentation of a new, improved model, allowing more confident evaluation of the contributions from different NW destructive forces to RCI formation, thus leading to more accurate approximation of the zone around the epicentre for a guided search for RCI cases. MATERIALS AND METHODS The model is made compatible with a classic approach and provides the estimates of radial distance from the epicenter, at which NW explosion can produce RCI. Mathematical formalism comprises a set of equations for...
Radiation Protection Dosimetry, 1997
Lymphocytes from some evacuees from Prypiat and clean-up workers (liquidators) have been studied ... more Lymphocytes from some evacuees from Prypiat and clean-up workers (liquidators) have been studied for chromosomal aberrations. When dicentric yields from subjects are pooled in various ways, by date of evacuation, date of working at Chemobyl or delay in blood sampling, the resultant mean dose estimates are higher than have been generally assumed from dose reconstructions for Prypiat citizens or personal dosemeters worn by liquidators. Some of this difference may be due to the selection of subjects for study. However, dicentrics in one cohort of randomly selected evacuees, sampled very promptly, indicated a mean dose of ∼300 mGy which is significantly in excess of mean dose reconstructions of ∼10-20 mSv.
Genome Integrity
be performed successfully only if the aberration scoring has been done with sufficient accuracy. ... more be performed successfully only if the aberration scoring has been done with sufficient accuracy. [3] The optimization of uncertainties in dose estimates through defining the required numbers of metaphases scored and aberrations found has been effectively resolved for low-dose radiation exposures using an expertise mode (manual microscope scoring of 1000 cells per sample) of cytogenetic analysis [4] and to some extent for a wider dose range of homogeneous exposure. [5] However, with one exception, [3] no such attempt has been made for partial-body exposure scenarios. There are a growing number of reports regarding triage biodosimetry of partial-body exposures performed in experiments with in vitro simulations. [6-12] These studies focused mainly on the accuracy of dose estimates and their efficacy in classifying samples between triage categories. Much less information can be found in the literature regarding the speed of collecting the necessary number of metaphases or aberrations in scenarios of inhomogeneous exposure. Furthermore, many authors presented comparisons of the accuracy of manual and automated cytogenetic analysis, but only a few studies [8,13] showed
Dosimetric biomarkers have been effectively and intensively used for a long time in the area of r... more Dosimetric biomarkers have been effectively and intensively used for a long time in the area of radiation protection. In contrast to that, no robust standards or widely accepted protocols for application of these end-points in radiotherapy, diagnostic and interventional radiology and nuclear medicine exist to date. The International Atomic Energy Agency (IAEA) organized the review of the available data on the possibilities of the use of dosimetric biomarkers in medical irradiation scenarios. The resultant Technical Report also contains a summary of identified problems, gaps in knowledge, limitations in methodology and recommendations for their overcoming. This work provided a conceptual background for the initiation of a new IAEA Coordinated Research Project E35010, MEDBIODOSE (2017-21), which is aimed specifically at the development and improvement of applications of biodosimetric markers in clinical practice.
Journal of Personalized Medicine
A search for effective methods for the assessment of patients’ individual response to radiation i... more A search for effective methods for the assessment of patients’ individual response to radiation is one of the important tasks of clinical radiobiology. This review summarizes available data on the use of ex vivo cytogenetic markers, typically used for biodosimetry, for the prediction of individual clinical radiosensitivity (normal tissue toxicity, NTT) in cells of cancer patients undergoing therapeutic irradiation. In approximately 50% of the relevant reports, selected for the analysis in peer-reviewed international journals, the average ex vivo induced yield of these biodosimetric markers was higher in patients with severe reactions than in patients with a lower grade of NTT. Also, a significant correlation was sometimes found between the biodosimetric marker yield and the severity of acute or late NTT reactions at an individual level, but this observation was not unequivocally proven. A similar controversy of published results was found regarding the attempts to apply G2- and γH2A...
Applied Radiation and Isotopes
Scientific reports, Jan 12, 2018
Previous investigations in gene expression changes in blood after radiation exposure have highlig... more Previous investigations in gene expression changes in blood after radiation exposure have highlighted its potential to provide biomarkers of exposure. Here, FDXR transcriptional changes in blood were investigated in humans undergoing a range of external radiation exposure procedures covering several orders of magnitude (cardiac fluoroscopy, diagnostic computed tomography (CT)) and treatments (total body and local radiotherapy). Moreover, a method was developed to assess the dose to the blood using physical exposure parameters. FDXR expression was significantly up-regulated 24 hr after radiotherapy in most patients and continuously during the fractionated treatment. Significance was reached even after diagnostic CT 2 hours post-exposure. We further showed that no significant differences in expression were found between ex vivo and in vivo samples from the same patients. Moreover, potential confounding factors such as gender, infection status and anti-oxidants only affect moderately F...
Radiation Protection Dosimetry, Nov 25, 2013
Classical methods of assessing the uncertainty associated with radiation doses estimated using cy... more Classical methods of assessing the uncertainty associated with radiation doses estimated using cytogenetic techniques are now extremely well defined. However, several authors have suggested that a Bayesian approach to uncertainty estimation may be more suitable for cytogenetic data, which are inherently stochastic in nature. The Bayesian analysis framework focuses on identification of probability distributions (for yield of aberrations or estimated dose), which also means that uncertainty is an intrinsic part of the analysis, rather than an 'afterthought'. In this paper Bayesian, as well as some more advanced classical, data analysis methods for radiation cytogenetics are reviewed that have been proposed in the literature. A practical overview of Bayesian cytogenetic dose estimation is also presented, with worked examples from the literature.
Http Dx Doi Org 10 1667 Rr2228 1, Jul 14, 2010
The scientific literature concerning cytogenetic biodosimetry has been reviewed to identify the r... more The scientific literature concerning cytogenetic biodosimetry has been reviewed to identify the range of scenarios of radiation exposure where biodosimetry has been carried out. Limitations in the existing standardized statistical methodology have been identified and categorized, and the reasons for these limitations have been explored. Statistical problems generally occur due to either low numbers of aberrations leading to large uncertainties or deviations in aberration-per-cell distributions leading to over- or under-dispersion with respect to the Poisson model. A number of difficulties also stem from limitations of the classical statistical methodology, which requires that chromosome aberration yields be considered as something "fixed" and thus provides a deterministic estimate of radiation dose and associated confidence limits (because an assignment of a probability to an event is based solely on the observed frequency of occurrence of the event). Therefore, it is suggested that solutions to the listed problems should be based in the Bayesian framework. This will allow the investigator to take a probabilistic approach to analysis of cytogenetic data, which can be considered highly appropriate for biological dose estimation.