A New Model of Biodosimetry to Integrate Low and High Doses

Biological dosimetry, that is the estimation of the dose of an exposure to ionizing radiation by a biological parameter, is a very important tool in cases of radiation accidents. The score of dicentric chromosomes, considered to be the most accurate method for biological dosimetry, for low LET radiation and up to 5 Gy, fits very well to a linear-quadratic model of dose-effect curve assuming the Poisson distribution. The accuracy of this estimation raises difficulties for doses over 5 Gy,the highest dose of the majority of dose-effect curves used in biological dosimetry. At doses over 5 Gy most cells show difficulties in reaching mitosis and cannot be used to score dicentric chromosomes. In the present study with the treatment of lymphocyte cultures with caffeine and the standardization of the culture time, metaphases for doses up to 25 Gy have been analyzed. Here we present a new model for biological dosimetry, which includes a Gompertz-type function as the dose response, and also takes into account the underdispersion of aberrationamong-cell distribution. The new model allows the estimation of doses of exposures to ionizing radiation of up to 25 Gy. Moreover, the model is more effective in estimating whole and partial body exposures than the classical method based on linear and linear-quadratic functions, suggesting their effectiveness and great potential to be used after high dose exposures of radiation

Dosimetria biològica per exposicions a altes dosis de radiació ionitzant i exposicions heterogènies

La dosimetria biològica permet estimar la dosi d'una exposició a radiacions ionitzants mitjançant l'anàlisi d'un biomarcador, i és un element imprescindible en el camp de la radioprotecció. Entre els diferents biomarcadors que es poden utilitzar, els cromosomes dicèntrics presents en metafases de limfòcits de sang perifèrica, es consideren els més útils ja que la seva freqüència s'ajusta acuradament a les variacions de dosi. Això és cert per dosis fins 4-5 Gy, a dosis superiors el nombre de cèl·lules que arriben a metafase és molt petit dificultant-se molt l'anàlisi. Per superar aquesta limitació, la inhibició del checkpoint G2/M amb l'addició de cafeïna i la optimització de la durada del cultiu, ha permès mitigar el retard mitòtic, obtenint suficients metafases per a realitzar l'estudi citogenètic. Amb aquesta nova metodologia s'ha pogut establir una corba dosi-efecte amb dosis de fins a 25 Gy, basada en un model Gompertz (no utilitzat fins al moment en dosimetria biològica). La fiabilitat d'aquest model ha estat testat tan en simulacions d'irradiació total com parcial. Per altra banda, en molts accidents radiològics on la irradiació no és homogènia, fins el moment el seu estudi es basava en considerar que una part del cos havia estat irradiada homogèniament mentre que l'altre part no havia estat irradiada. Aquesta consideració resulta poc realista ja que a la majoria d'accidents, els individus exposats reben un gradient de dosis. Amb l'objectiu d'estudiar les exposicions heterogènies s'han fet simulacions barrejant sang irradiada d'un home i una dona a dues dosis diferents, amb aquesta metodologia s'ha pogut distingir l'origen de cadascuna de les cèl·lules analitzades. Mitjançant l'aplicació d'un model de mixtura de Poissons s'ha pogut determinar la freqüència de dicèntrics de cadascuna de les dues fraccions irradiades i estimar la dosi de radiació rebuda i la fracció inicial de cèl·lules irradiades a cada dosi. La possibilitat de poder estimar dosis altes de radiació, així com poder diferenciar millor les irradiacions no homogènies és una aportació molt important en el camp de la radioprotecció.Biological dosimetry allow us to estimate the dose to an exposure to ionizing radiation thought the analysis of a biomarker, and is an essential element in radiation protection. Among various biomarkers that can be used, dicentric chromosomes in metaphase from peripheral blood lymphocytes are considered the most useful, because their frequency is correlated in variations of the dose. This is true for doses up to 4-5 Gy, in higher doses the numbers of cells that achieve metaphase are very few and for this reason analysis becomes increasingly difficult. To overcome this limitation, the inhibition of the G2/M checkpoint by the addition of caffeine and the optimization of the culture duration, allows the mitigation of the mitotic delay, getting enough metaphases to perform the cytogenetic analysis. Through this methodology, a dose effect curve has been established for doses up to 25 Gy, it is based in a Gompertz model (that has never been used so far in biological dosimetry). The reliability of this model has been tested for whole and partial simulations. Furthermore, in most of radiological accidents where the irradiation is not homogeneous, up to now, its study was based in considering that one part of the body had been irradiated while the other part had not. This consideration becomes unrealistic because in the majority of accidents the exposed individuals received a gradient of doses. In order to study the heterogeneous exposures simulations, mixing irradiated blood at two different doses from a male and a female, allows the differentiation of the origin of each analyzed cell. Through the application of a mixture Poisson model the dicentric frequency from each fraction has been determined as well as the received dose and the initial proportion of cells irradiated at each dose. The possibility to estimate the received dose after high doses of exposure, as well as the better differentiation for the study of non homogeneous exposures is a very important contribution to the radioprotection field

DNA damage response in peripheral mouse blood leukocytes in vivo after variable, low-dose rate exposure.

Environmental contamination and ingestion of the radionuclide Cesium-137 (137Cs) is a large concern in fallout from a nuclear reactor accident or improvised nuclear device, and highlights the need to develop biological assays for low-dose rate, internal emitter radiation. To mimic low-dose rates attributable to fallout, we have developed a VAriable Dose-rate External 137Cs irradiatoR (VADER), which can provide arbitrarily varying and progressive low-dose rate irradiations in the range of 0.1-1.2 Gy/day, while circumventing the complexities of dealing with radioactively contaminated biomaterials. We investigated the kinetics of mouse peripheral leukocytes DNA damage response in vivo after variable, low-dose rate 137Cs exposure. C57BL/6 mice were placed in the VADER over 7 days with total accumulated dose up to 2.7 Gy. Peripheral blood response including the leukocyte depletion, apoptosis as well as its signal protein p53 and DNA repair biomarker γ-H2AX was measured. The results illustrated that blood leukocyte numbers had significantly dropped by day 7. P53 levels peaked at day 2 (total dose = 0.91 Gy) and then declined; whereas, γ-H2AX fluorescence intensity (MFI) and foci number generally increased with accumulated dose and peaked at day 5 (total dose = 2.08 Gy). ROC curve analysis for γ-H2AX provided a good discrimination of accumulated dose < 2 Gy and ≥ 2 Gy, highlighting the potential of γ-H2AX MFI as a biomarker for dosimetry in a protracted, environmental exposure scenario

VADER: a variable dose-rate external 137Cs irradiator for internal emitter and low dose rate studies.

In the long term, 137Cs is probably the most biologically important agent released in many accidental (or malicious) radiation disasters. It can enter the food chain, and be consumed, or, if present in the environment (e.g. from fallout), can provide external irradiation over prolonged times. In either case, due to the high penetration of the energetic γ rays emitted by 137Cs, the individual will be exposed to a low dose rate, uniform, whole body, irradiation. The VADER (VAriable Dose-rate External 137Cs irradiatoR) allows modeling these exposures, bypassing many of the problems inherent in internal emitter studies. Making use of discarded 137Cs brachytherapy seeds, the VADER can provide varying low dose rate irradiations at dose rates of 0.1 to 1.2 Gy/day. The VADER includes a mouse "hotel", designed to allow long term simultaneous residency of up to 15 mice. Two source platters containing ~ 250 mCi each of 137Cs brachytherapy seeds are mounted above and below the "hotel" and can be moved under computer control to provide constant low dose rate or a varying dose rate mimicking 137Cs biokinetics in mouse or man. We present the VADER design and characterization of its performance over 18 months of use

A New Model of Biodosimetry to Integrate Low and High Doses

Biological dosimetry, that is the estimation of the dose of an exposure to ionizing radiation by a biological parameter, is a very important tool in cases of radiation accidents. The score of dicentric chromosomes, considered to be the most accurate method for biological dosimetry, for low LET radiation and up to 5 Gy, fits very well to a linear-quadratic model of dose-effect curve assuming the Poisson distribution. The accuracy of this estimation raises difficulties for doses over 5 Gy,the highest dose of the majority of dose-effect curves used in biological dosimetry. At doses over 5 Gy most cells show difficulties in reaching mitosis and cannot be used to score dicentric chromosomes. In the present study with the treatment of lymphocyte cultures with caffeine and the standardization of the culture time, metaphases for doses up to 25 Gy have been analyzed. Here we present a new model for biological dosimetry, which includes a Gompertz-type function as the dose response, and also takes into account the underdispersion of aberrationamong-cell distribution. The new model allows the estimation of doses of exposures to ionizing radiation of up to 25 Gy. Moreover, the model is more effective in estimating whole and partial body exposures than the classical method based on linear and linear-quadratic functions, suggesting their effectiveness and great potential to be used after high dose exposures of radiation

RENEB Inter-Laboratory Comparison 2021: The FISH-Based Translocation Assay

10.1667/RADE-22-00203.1Radiation Research1996583-59

Supplementary Material for: International comparison exercise for biological dosimetry after exposures with neutrons performed at two irradiation facilities as part of the BALANCE project

In the case of a radiological or nuclear event, biological dosimetry can be an important tool to support clinical decision-making. During a nuclear event, individuals might be exposed to a mixed field of neutrons and photons. The composition of the field and the neutron energy spectrum influence the degree of damage to the chromosomes. During the transatlantic BALANCE project, an exposure similar to a Hiroshima-like device at a distance of 1.5 km from the epicenter was simulated and biological dosimetry based on dicentric chromosomes was performed to evaluate the participants ability to discover unknown doses and to test the influence of differences in neutron spectra. In a first step, calibration curves were established by irradiating blood samples with 5 doses in the range of 0 Gy to 4 Gy at two different facilities in Germany (PTB) and USA (CINF). The samples were sent to eight participating laboratories from the RENEB network and dicentric chromosomes were scored by each participant. Next, blood samples were irradiated with 4 blind doses in each of the two facilities and sent to the participants to provide dose estimates based on the established calibration curves. Manual and semi-automatic scoring of dicentric chromosomes were evaluated for their applicability to neutron exposures. Moreover, the biological effectiveness of the neutrons from the two irradiation facilities was compared. The calibration curves from samples irradiated at CINF showed a 1.4 times higher biological effectiveness compared to samples irradiated at PTB. For manual scoring of dicentric chromosomes, the doses of the test samples were mostly successfully resolved based on the calibration curves established during the project. For semi-automatic scoring, the dose estimation for the test samples was less successful. Doses >2 Gy in the calibration curves revealed non-linear associations between dose and dispersion index of the dicentric counts, especially for manual scoring. The differences in the biological effectiveness between the irradiation facilities suggested that the neutron energy spectrum can have a strong impact on the dicentric counts

Supplementary Material for: International comparison exercise for biological dosimetry after exposures with neutrons performed at two irradiation facilities as part of the BALANCE project

In the case of a radiological or nuclear event, biological dosimetry can be an important tool to support clinical decision-making. During a nuclear event, individuals might be exposed to a mixed field of neutrons and photons. The composition of the field and the neutron energy spectrum influence the degree of damage to the chromosomes. During the transatlantic BALANCE project, an exposure similar to a Hiroshima-like device at a distance of 1.5 km from the epicenter was simulated and biological dosimetry based on dicentric chromosomes was performed to evaluate the participants ability to discover unknown doses and to test the influence of differences in neutron spectra. In a first step, calibration curves were established by irradiating blood samples with 5 doses in the range of 0 Gy to 4 Gy at two different facilities in Germany (PTB) and USA (CINF). The samples were sent to eight participating laboratories from the RENEB network and dicentric chromosomes were scored by each participant. Next, blood samples were irradiated with 4 blind doses in each of the two facilities and sent to the participants to provide dose estimates based on the established calibration curves. Manual and semi-automatic scoring of dicentric chromosomes were evaluated for their applicability to neutron exposures. Moreover, the biological effectiveness of the neutrons from the two irradiation facilities was compared. The calibration curves from samples irradiated at CINF showed a 1.4 times higher biological effectiveness compared to samples irradiated at PTB. For manual scoring of dicentric chromosomes, the doses of the test samples were mostly successfully resolved based on the calibration curves established during the project. For semi-automatic scoring, the dose estimation for the test samples was less successful. Doses >2 Gy in the calibration curves revealed non-linear associations between dose and dispersion index of the dicentric counts, especially for manual scoring. The differences in the biological effectiveness between the irradiation facilities suggested that the neutron energy spectrum can have a strong impact on the dicentric counts

RENEB Inter-Laboratory Comparison 2021: The Dicentric Chromosome Assay

10.1667/RADE-22-00202.1Radiation Research1996556–57

Programa d’optimització d’antibiòtics: infeccions del tracte urinari en adults

Antibiòtics; Infeccions; Tracte urinari; AdultsAntibiotics; Infections; Urinary tract; AdultsAntibióticos; Infecciones; Tracto urinario; AdultosAl document s’hi aborden les principals infeccions del tracte urinari, es descriuen les recomanacions i accions a dur a terme abans de prescriure un antibiòtic i se n’estableixen criteris de tractament, seguiment i derivació