Equivalent Whole-body Dose Research Articles

Estimating partial-body ionizing radiation exposure by automated cytogenetic biodosimetry

Purpose Inhomogeneous exposures to ionizing radiation can be detected and quantified with the dicentric chromosome assay (DCA) of metaphase cells. Complete automation of interpretation of the DCA for whole-body irradiation has significantly improved throughput without compromising accuracy, however, low levels of residual false positive dicentric chromosomes (DCs) have confounded its application for partial-body exposure determination. Materials and methods We describe a method of estimating and correcting for false positive DCs in digitally processed images of metaphase cells. Nearly all DCs detected in unirradiated calibration samples are introduced by digital image processing. DC frequencies of irradiated calibration samples and those exposed to unknown radiation levels are corrected subtracting this false positive fraction from each. In partial-body exposures, the fraction of cells exposed, and radiation dose can be quantified after applying this modification of the contaminated Poisson method. Results Dose estimates of three partially irradiated samples diverged 0.2–2.5 Gy from physical doses and irradiated cell fractions deviated by 2.3%–15.8% from the known levels. Synthetic partial-body samples comprised of unirradiated and 3 Gy samples from 4 laboratories were correctly discriminated as inhomogeneous by multiple criteria. Root mean squared errors of these dose estimates ranged from 0.52 to 1.14 Gy2 and from 8.1 to 33.3%2 for the fraction of cells irradiated. Conclusions Automated DCA can differentiate whole- from partial-body radiation exposures and provides timely quantification of estimated whole-body equivalent dose.

Measurement of γ-H2AX foci, miRNA-101, and gene expression as a means to quantify radiation-absorbed dose in cancer patients who had undergone radiotherapy.

Radiological accidents and nuclear terrorism pose an increased threat to members of the public who, following such an event, would need to be assessed for medical care by fast triage. Assay methods such as chromosome aberrations (CA), cytokinesis-block micronucleus (CBMN) and fluorescence in situ hybridization (FISH) techniques have been well established for dose estimation and their potential for handling more samples has also been proved with automation. However, culturing of lymphocytes is an inevitable step, which limits the potential of these markers for triage. In vitro analysis of gamma-H2AX (γ-H2AX), gene and microRNA (miRNA) markers do not require culturing of lymphocytes, and as such have been suggested as attractive tools for triage. Despite studies reporting in vitro dose-response curves, limited evidence is available evaluating the suitability of these assays in real situations. In this study, we have measured the absorbed dose using γ-H2AX, gene (GADD45A, FDXR, and CDKN1A) and miRNA-101 expression in blood samples of cancer patients (n = 20) who had undergone partial-body radiotherapy and compared with the derived equivalent whole-body doses (EWBD). The obtained results from all patients showed a significant (p < 0.05) increase of γ-H2AX foci in post-irradiated as compared to pre-irradiated samples. Moreover, estimated doses using γ-H2AX foci showed a correlation with the derived EWBD (r2 = 0.60, p = 0.0003) and was also shown to be dependent on the irradiated body volume. Consistent with γ-H2AX foci frequency, an increase in fold change expression of genes and miRNA-101 was observed. However, the estimated dose significantly varied among the subjects and showed poor correlation (r2 = 0.09, 0.04, 0.01 and 0.03 for GADD45A, FDXR, CDKN1A and miRNA-101, respectively) with EWBD. The overall results suggest that the established in vitro γ-H2AX assay is suitable for the detection of radiation exposure and can also provide an estimate of the dose in in vivo irradiated samples. The genes and miRNA-101 markers showed increased expression; nevertheless, there is a need for further improvements to measure doses accurately using these markers.

P286] Study on semi-automatically evaluated micronucleus frequency changes in patients with prostate adenocarcinoma undergoing low and high dose rate brachytherapy

Purpose We compared the biological damaging effect of low and high dose rate brachytherapy (LDR and HDR) in healthy tissues of patients with prostate adenocarcinoma by following up the changes of DNA damage with cytokinesis-blocked micronucleus assay (CBMN) during and after the treatment. Methods The CBMN assay was proven by literature to be good indicator of received dose during partial-body radiotherapy. The first blood samples were collected preceding the radiation therapy and the next ones in regular intervals after the seed insertion (LDR) or the end of treatment (HDR) (once every 3 month during the first year). The automatic analysis (scanning and image processing) was conducted by a dedicated totally automatized microscopic system. Results We determined the MN frequency of 5 patients from each treatment group automatically and manually as well. We found that in order to ensure the reliability of the comparison of automatic scoring results an extra step has to be introduced for sample quality improvement. This way the tendency of MN frequency versus elapsed time became possible to be accurately identified and analysed for both brachytherapy techniques. Due to the relatively low whole-body equivalent dose, the best results were achieved with the user-supervised semi-automatic combined method which merges the advantages of the accuracy of manual revision and the rapidity of the automation. Conclusions Although the signal is comparable with the order of changes, the automation-aided evaluation decreased the achieved uncertainty and made it possible to identify a definite and significant tendency in the change of MN frequency for LDR and HDR as well. Acknowledgment This work has been carried out in the frame of VKSZ 14-1-2015-0021 Hungarian project supported by the National Research, Development and Innovation Fund.

Comparison of whole-body equivalent doses from volumetric modulated arc therapy and static intensity-modulated radiotherapy for cervical cancer

Objective To compare the whole-body equivalent doses from volumetric modulated arc therapy (VMAT) and static intensity-modulated radiotherapy (IMRT) for patients with cervical cancer. Methods Nine patients with cervical cancer admitted to our hospital in 2014 were included in this study. Both VMAT and IMRT were planned for each patient. Each patient’s personal dose equivalent (Hp (10)) was measured using thermoluminescent dosimeters placed at the xiphoid process and glabella during IMRT and VMAT. The whole-body equivalent doses were estimated based on the results measured at the xiphoid process and compared between the VMAT and IMRT techniques. The paired t test was used for difference analysis. Results The Hp (10) values measured at the xiphoid process and glabella of every patient were lower for VMAT than for IMRT. At a prescribed dose of 50 Gy, if the mean Hp (10) values measured at the xiphoid process were considered to represent the whole-body equivalent doses, the whole-body equivalent doses for VMAT and IMRT were 364 mSv and 538 mSv, respectively. Conclusions VMAT results in a lower whole-body equivalent dose to patients compared with IMRT. The decreased whole-body equivalent dose delivered by VMAT may reduce the likelihood of a radiation-induced secondary malignancy. Key words: Cervical neoplasms/volumetric modulated arc therapy; Cervical neoplasms/intensity modulated radiation therapy; Whole-body equivalent dose

Biodosimetry Based on γ-H2AX Quantification and Cytogenetics after Partial- and Total-Body Irradiation during Fractionated Radiotherapy.

The aim of this current study was to quantitatively describe radiation-induced DNA damage and its distribution in leukocytes of cancer patients after fractionated partial- or total-body radiotherapy. Specifically, the impact of exposed anatomic region and administered dose was investigated in breast and prostate cancer patients receiving partial-body radiotherapy. DNA double-strand breaks (DSBs) were quantified by γ-H2AX immunostaining. The frequency of unstable chromosomal aberrations in stimulated lymphocytes was also determined and compared with the frequency of DNA DSBs in the same samples. The frequency of radiation-induced DNA damage was converted into dose, using ex vivo generated calibration curves, and was then compared with the administered physical dose. This study showed that 0.5 h after partial-body radiotherapy the quantity of radiation-induced γ-H2AX foci increased linearly with the administered equivalent whole-body dose for both tumor entities. Foci frequencies dropped 1 day thereafter but proportionality to the equivalent whole-body dose was maintained. Conversely, the frequency of radiation-induced cytogenetic damage increased from 0.5 h to 1 day after the first partial-body exposure with a linear dependence on the administered equivalent whole-body dose, for prostate cancer patients only. Only γ-H2AX foci assessment immediately after partial-body radiotherapy was a reliable measure of the expected equivalent whole-body dose. Local tumor doses could be approximated with both assays after one day. After total-body radiotherapy satisfactory dose estimates were achieved with both assays up to 8 h after exposure. In conclusion, the quantification of radiation-induced γ-H2AX foci, but not cytogenetic damage in peripheral leukocytes was a sensitive and rapid biodosimeter after acute heterogeneous irradiation of partial body volumes that was able to primarily assess the absorbed equivalent whole-body dose.

Assessment of Total- and Partial-Body Irradiation in a Baboon Model

This biodosimetry study used irradiated baboons to investigate the efficacy of a kinetic multiparameter (clinical, physical, and biological) approach for discriminating partial-body irradiation (PBI) and total-body irradiation (TBI). Animals were unilaterally (front) exposed to 60Co gamma rays (8 to 32 cGy min) using either TBI or vertical left hemi-body irradiation (HBI), as follows: 2.5 Gy TBI (n = 2), 5 Gy TBI (n = 2), 5 Gy HBI (n = 2), and 10 Gy HBI (n = 2). Midline tissue doses were measured at the anterior iliac crest level with an ionization chamber, and body dosimetry was performed using thermoluminescent dosimeters. Blood samples were collected before exposure and from 1 h until 200 d after irradiation. Clinical status, complete blood cell count, biochemical parameters, and cytogenetic analysis were evaluated. The partial least square discriminant analysis chosen for statistical analysis showed that the four groups of irradiated baboons were clearly separated. However, the dicentric chromosome assay may not distinguish HBI from TBI in confounding situations where equivalent whole-body doses are similar and the time of exposure is sufficient for peripheral blood lymphocyte homogenization. Interestingly, as bone marrow shielding in HBI animals prevented aplasia from happening, hematologic parameters such as the platelet count and Flt-3 ligand level helped to distinguish HBI and TBI. Moreover, the ratio of neutrophil to lymphocyte counts, creatine kinase, and citrulline levels may be discriminating biomarkers of dose or injury. Both early and delayed clinical signs and bioindicators appear to be useful for assessment of heterogeneous irradiation.

The association of DNA-dependent protein kinase activity of peripheral blood lymphocytes with prognosis of cancer

Background:Repair of various types of DNA damages is critical for genomic stability. DNA-dependent protein kinase (DNA-PK) has an important role in DNA double-strand break repair. We examined whether there may be a correlation between DNA-PK activity in peripheral blood lymphocytes (PBLs) and survival percentages in various cancer patients. We also investigated the changes of DNA-PK activity in PBLs after radiotherapy.Methods:A total of 167 of untreated cancer patients participated in this study. Peripheral blood was collected, separated, and centrifuged. DNA-PK activity was measured by DNA-pull-down assay. Chromosomal aberrations were examined by cytogenetic methods.Results:DNA-PK activity of PBLs in advanced cancer patients was significantly lower than that in early stage. The patients with lower DNA-PK activity in PBLs tended to have the lower disease-specific survivals and distant metastasis-free survivals than those with higher DNA-PK activity in advanced stages. There was also a tendency of inverse correlation between DNA-PK activity and excess fragments. The DNA-PK activity of PBLs in most patients decreased in response to radiation as the equivalent whole-body dose increased.Conclusion:Cancer patients in advanced stage, with lower DNA-PK activity of PBLs might have higher distant metastasis and exhibit poorer prognosis. Therefore, DNA-PK activity in PBLs could be used as a marker to predict the chromosomal instability and poorer prognosis.

Human Biodistribution and Dosimetry of the PET Radioligand [11C]Flumazenil (FMZ)

We measure the whole-body distribution of IV injected [¹¹C]Flumazenil (FMZ) as a function of time in adult subjects and determine the absorbed radiation doses. After injection with 770 MBq of [¹¹C]FMZ (nominal), each of six subjects underwent nine consecutive whole body PET scans. Twelve source organs were identified using PET attenuation and emission images. Activity within each organ as a function of time was determined from the sequence of the nine PET scans. Source organ time activity curves were integrated and normalized by the injected dose to yield source organ residence times for the no voiding situation. Separate bladder residence-time calculations were performed for the cases of a 1- and a 2-h voiding interval. Using the source organ residence times as input, the program OLINDA/EXM (Stabin et al. in J Nucl Med. 46:1023-1027, 2005) was used to perform dosimetry calculations for the various body organs and for the whole body. For the no voiding situation, the average whole-body radiation equivalent dose was 3.02 × 10⁻³ mSv/MBq of injected [¹¹C]FMZ. The average effective dose and effective dose equivalent was 7.57 × 10⁻³ and 1.12 × 10⁻² mSv MBq⁻¹, respectively. The organ receiving the highest equivalent dose was the urinary bladder wall with an average of 6.32 × 10⁻² mSv MBq⁻¹. On average, the administration of less than 790 MBq (21 mCi) of [¹¹C]FMZ yields (no voiding model) an organ equivalent dose of under 50 mSv [the single dose limit for research studies under US regulations (21CFR361.1) to body organs other than blood forming organs, gonads or the lens of the eye] to all organs. Equivalent dose to the blood forming organs and gonads from a 790 MBq administered FMZ dose is well under the 30 mSv limit provided under 21CFR361.1. Additionally, administration of less than 1320 MBq (35.7 mCi) yields an effective dose [International Commission on Radiation Protection (ICRP) 60 tissue weighting scheme] of under 10 mSv, which is the ICRP IIb (minor to intermediate) risk category limit.

A Verification of Treatment Protocol in Fractionated Radiotherapy by Biological Dosimetry

In radiation therapy of cancer, any possible mistakes that may occur in prescribed tumour dose calculation and/ or in treatment set up could also be checked by the biological dosimetry. In order to verify this, 20 patients having pelvic area tumours with no prescribed chemotherapy were selected. Their peripheral blood samples were collected before starting fractionated radiotherapy and at some definite time during treatment. Equivalent whole body doses (EWBD) were calculated from patient’s weights, irradiated volumes and total tumor doses given until the date of blood sample collection during treatment. Each patient’s EWBD was given in vitro to blood samples that were collected before starting radiotherapy. Radiation induced chromosome damage in lymphocytes were measured by micronucleus (MN) induction. The relationship between the micronucleus frequencies (MN/BN) scored during therapy ( in vivo ) and the micronucleus frequencies scored after the application of in vitro EWBD was investigated. MN/BN rates scored following in vitro application of EWBD differed between 0.195 and 0.540, whereas MN/BN rates obtained during radiotherapy equivalent to EWBD differed between 0.213 and 0.625. It was shown that there was no significant difference (p=0.653) between the MN scores following in vitro applied EWBD and MN scores obtained in vivo . The existence of this correlation has confirmed the correct application of fractionated radiotherapy and treatment setup for the patients.

Cytogenetic assessment of heterogeneous radiation doses in cancer patients treated with fractionated radiotherapy

The purpose of this study was to evaluate the in vivo dose-response relation of chromosome aberration formation and distribution in a context of localised and fractionated radiotherapy. Cytogenetic analysis was applied to eight patients, all treated for the same tumour localisation; the same localisation was used to prevent the variability usually observed between patients treated with radiotherapy and to allow the corresponding roles of the size of irradiation field and of the dose rate to be studied. The yield of dicentrics, centric rings and fragments was measured in blood samples taken before treatment, during the course of radiotherapy and up to 6 months after. After the first fraction of radiotherapy, we observed that the whole-body dose estimated from the yield of dicentrics and rings was higher (0.35+/-0.2 Gy) than the calculated equivalent whole-body dose (0.07+/-0.04 Gy). By contrast, the partial-body dose derived from the Qdr (quotient of dicentrics and rings) model was estimated to be 2.2+/-0.3 Gy, which agreed quite well with the dose delivered to the tumour (2.1+/-0.1 Gy). We also found a correlation between the yield of induced chromosome aberrations and the target field size (p = 0.014). U-value analysis showed that the distribution of dicentrics and rings was overdispersed, despite the fractionation of the exposure, and a positive correlation between the U-value and the dose rate was observed (p = 0.017). Overall, these results suggest that the proportion of undamaged lymphocytes could increase with the dose rate.

Cytogenetic assessment of heterogeneous radiation doses in cancer patients treated with fractionated radiotherapy

The purpose of this study was to evaluate the in vivo dose-response relation of chromosome aberration formation and distribution in a context of localised and fractionated radiotherapy. Cytogenetic analysis was applied to eight patients, all treated for the same tumour localisation; the same localisation was used to prevent the variability usually observed between patients treated with radiotherapy and to allow the corresponding roles of the size of irradiation field and of the dose rate to be studied. The yield of dicentrics, centric rings and fragments was measured in blood samples taken before treatment, during the course of radiotherapy and up to 6 months after. After the first fraction of radiotherapy, we observed that the whole-body dose estimated from the yield of dicentrics and rings was higher (0.35+/-0.2 Gy) than the calculated equivalent whole-body dose (0.07+/-0.04 Gy). By contrast, the partial-body dose derived from the Qdr (quotient of dicentrics and rings) model was estimated to be 2.2+/-0.3 Gy, which agreed quite well with the dose delivered to the tumour (2.1+/-0.1 Gy). We also found a correlation between the yield of induced chromosome aberrations and the target field size (p = 0.014). U-value analysis showed that the distribution of dicentrics and rings was overdispersed, despite the fractionation of the exposure, and a positive correlation between the U-value and the dose rate was observed (p = 0.017). Overall, these results suggest that the proportion of undamaged lymphocytes could increase with the dose rate.

COHN analysis: Body composition measurements based on the associated particle imaging and prompt-gamma neutron activation analysis techniques

The measurement of the body’s carbon (C), oxygen (O), hydrogen (H), and nitrogen (N) content can be used to calculate the relative amounts of fat, protein, and water. A system based on prompt-gamma neutron activation analysis (PGNAA), coupled with the associated particle imaging (API) technique, is being developed for this purpose. A compact D,T neutron generator (~10 7 n/s output) with an internal alpha-particle detector is used. The counting system consists of 6 shielded bismuth germanate (BGO) detectors (10.2 cmu10.2 cmu10.2 cm) operated with fast-timing electronics to detect only gamma-rays within a 100 ns time window following a trigger pulse generated by the alpha detector. The body can be scanned from the shoulders to the knees within about 30 min, with the equivalent whole-body dose <0.4 mSv. The cumulative gamma-ray spectra in the 2 MeV to 8 MeV region is collected and analyzed for multiple peaks attributed to body C,O,H, and N. Measurement precision for each element, based on tissue-equivalent phantoms, are in the 2–5% range, which are sufficient for population studies in adults. Further improvements are needed to extend the measurements to pediatric clinical research studies.

Biodosimetry using chromosome aberrations in human lymphocytes

In vitro dose-response calibration curves for (60)Co gamma rays have been established for unstable chromosome aberrations in human peripheral blood lymphocytes. The observed dose-response data were fitted to a linear quadratic model. The calibration curve parameters were used to estimate the equivalent whole-body dose and dose to the irradiated region in partial body irradiation of cancer patients. The derived partial body doses and fractions of lymphocytes irradiated were in agreement with those estimated from the radiotherapy regimes.

Energy modulated electron therapy using a few leaf electron collimator in combination with IMRT and 3D‐CRT: Monte Carlo‐based planning and dosimetric evaluation

Energy modulated electron therapy (EMET) based on Monte Carlo dose calculation is a promising technique that enhances the treatment planning and delivery of superficially located tumors. This study investigated the application of EMET using a novel few-leaf electron collimator (FLEC) in head and neck and breast sites in comparison with three-dimensional conventional radiation therapy (3D-CRT) and intensity modulated radiation therapy (IMRT) techniques. Treatment planning was performed for two parotid cases and one breast case. Four plans were compared for each case: 3D-CRT, IMRT, 3D-CRT in conjunction with EMET (EMET-CRT), and IMRT in conjunction with EMET (EMET-IMRT), all of which were performed and calculated with Monte Carlo techniques. For all patients, dose volume histograms (DVHs) were obtained for all organs of interest and the DVHs were used as a means of comparing the plans. Homogeneity and conformity of dose distributions were calculated, as well as a sparing index that compares the effect of the low isodose lines. In addition, the whole-body dose equivalent (WBDE) was estimated for each plan. Adding EMET delivered with the FLEC to 3D-CRT improves sparing of normal tissues. For the two head and neck cases, the mean dose to the contralateral parotid and brain stem was reduced relative to IMRT by 43% and 84%, and by 57% and 71%, respectively. Improved normal tissue sparing was quantified as an increase in sparing index of 47% and 30% for the head and neck and the breast cases, respectively. Adding EMET to either 3D-CRT or IMRT results in preservation of target conformity and dose homogeneity. When adding EMET to the treatment plan, the WBDE was reduced by between 6% and 19% for 3D-CRT and by between 21% and 33% for IMRT, while WBDE for EMET-CRT was reduced by up to 72% when compared with IMRT. FLEC offers a practical means of delivering modulated electron therapy. Although adding EMET delivered using the FLEC results in perturbation of target conformity when compared to IMRT, it significantly improves normal tissue sparing while offering enhanced target conformity to the 3D-CRT planning. The addition of EMET systematically leads to a reduction in WBDE especially when compared with IMRT.

MO-E-T-617-02: Dosimetric Evaluation of Inverse Monte Carlo-Based Modulated Electron Beam Treatment Planning and Delivery Using a Few Leaf Electron Collimator

Purpose: To investigate the potential of improving the treatment planning and delivery of treatment to superficially located tumors using energy modulated electron therapy (EMET) based on inverse techniques and Monte Carlo dose calculation algorithms. This study investigates the application of EMET using a few-leaf electron collimator (FLEC) in head & neck, sarcoma, and breast sites in comparison with three dimensional conventional radiation therapy (3D-CRT) and intensity modulated radiation therapy (IMRT) techniques. Method and Materials: Treatment planning was performed for a parotid case, a sarcoma case, and a breast case. Three Monte Carlo calculated plans were compared for each case: 3D-CRT, IMRT, and 3D-CRT in conjunction with EMET (EMET-CRT). For all patients, dose volume histograms (DVHs) were obtained for organs of interest. For each plan, homogeneity and conformity indices of dose distributions, sparing index (SPIN50/10) that quantifies the conformity of the low isodose lines, and the whole-body dose equivalent (WBDE) were analyzed. Results: Adding EMET delivered with the FLEC to 3D-CRT preserves target conformity and dose homogeneity and improves sparing of normal tissues. For the head & neck case the mean dose to the contralateral parotid and brain decreased relative to IMRT by 43% to 84%, and by 57% to 71%, respectively. Improved normal tissue sparing is also quantified as an increase in sparing index of 47% and 30% for the head & neck and the breast cases, respectively. The WBDE for EMET-CRT was reduced by up to 72% when compared with IMRT. Conclusion: EMET delivered with the FLEC could be a valuable addition to currently existing treatment techniques especially when applied to superficially located tumors that are inherently difficult to plan using IMRT. The addition of EMET systematically leads to a reduction in WBDE especially when compared with IMRT.

Noninvasive measurement of bone strontium.

The strontium content of bone has hitherto been impossible to measure noninvasively. A novel dual-photon absorptiometry (DPA) method was developed. 241Am (59.5 keV) and 133Ba (356 keV) were used as radiation sources. The linearity of the DPA method was studied in monkey bones ex vivo after treatment over 52 wk with strontium ranelate. The bone strontium expressed in terms of the percentage molar ratio SrHA/(SrHA + CaHA) x 100%, where HA denotes hydroxyapatite, was measured (1) by the DPA method and (2) by inductively coupled plasma-atomic emission spectrophotometry at the same distal site of the femur. The results correlated significantly: y = 0.33%Sr + 1.086x; r = 0.976; standard error of the estimate (SEE) = 0.57%Sr. In order to measure the accuracy error of Sr%, 30 normal volunteers were measured. Their mean values did not differ significantly from zero and the SD was 0.5%. The radiation dose was small, the equivalent whole-body dose to human subjects being 0.005 micro Sv. This novel DPA method is likely to be successful for bone strontium measurement in humans.

Cytogenetic monitoring of personnel working in angiocardiography laboratories in Iran hospitals

Angiocardiography is an X-ray examination of the blood vessels or chambers of the heart for evaluation of the number and severity of blockages in arteries that supply blood to the heart. Cardiologists and staff members applying these procedures are exposed to high levels of scattered radiation. In the present study we analyzed and followed-up on the cytogenetic effects of X-ray angiography in personnel of laboratories for treatment of cardiovascular disease. According to film dosimeter analysis, personnel received 0.25–15 mSv during the previous year (average of 3 mSv/y), which indicated an exposure below the limit established by the International Commission on Radiological Protection (ICRP). Samples of peripheral blood were collected from cardiologists, nurses and technicians and from a matched control group. The incidence of unstable chromosomal aberrations (dicentrics, acentric fragments, ring chromosomes) and cytokinesis-blocked micronuclei were analyzed. Results show a high frequency of acentric fragments in cardiologists, nurses and technicians compared to controls ( P < 0.001). When the exposed groups were compared, a higher percentage of acentric fragments was observed in the nurses and technicians compared to cardiologists ( P = 0.004). Six individuals presented with dicentric chromosomes and their equivalent whole-body doses ranged from 0.05 to 0.10 Gy. No correlation was observed between chromosome aberrations and annual effective dose or age of the exposed groups. Although the mean frequency of chromosome aberrations in the male workers was slightly higher than in the females, no significant difference was observed between male and female workers in each group ( P = 0.86). The mean number of micronuclei per 1000 binucleated cells was significantly higher in the exposed groups compared with the matched control group ( P < 0.001). In a follow-up study, chromosome aberrations in lymphocytes of 23 exposed personnel were analyzed five times during 3 years. Results show that the mean number of acentric fragments decreased gradually during 36 months in those workers who followed the radiation protection guides. The results of this study emphasize the importance of individual biomonitoring, limiting exposure and radiation safety programs.

Chromosomal biodosimetry by unfolding a mixed Poisson distribution: a generalized model

Purpose : The current chromosomal biodosimetry system is practically limited to the estimation of equivalent whole-body dose in the low or moderate dose range. To circumvent this problem, a new dosimetry system was developed which was effective over a wide dose range and dose gradient. Materials and methods : In order to establish a quantitative formalism of a comprehensive dose-response kinetics, chromosome aberration frequencies were studied in human peripheral blood lymphocytes irradiated in vitro with γ-rays in a dose range of 0.01-50Gy. Using the dose-yield relationship thus established, a new model of biodosimetry was developed which involved unfolding the chromosome aberration distribution into a mixed Poisson distribution and thence into a dose-distribution profile. The model was then tested with chromosome aberration data in lymphocytes irradiated in vitro, simulated partial body irradiation, accidental radiation exposure, therapeutic local irradiation and protracted exposure by internal deposit of Thorotrast. Results : The dose-yield relations over a wide dose range fit satisfactorily a multiparametric dose-response curve, which included the first approximation kinetics of linear-quadratic dose-response and its distortion by mutual interference among multiple breaks on a chromosome arm. The unfolding strategy using these dose-response kinetics was successfully applied to the various types of radiation exposures; the reconstructed dose profile showing a sharp unimodal peak for moderate or high doses of γ-rays in vitro irradiation, broadening for high-linear energy transfer radiation, discrimination of doses in the mixed culture of irradiated and unirradiated blood, and reasonable dose distribution for the in vivo exposures. Conclusion : A novel biodosimetry system was developed. The system is innovative in that it provides information not only on the macroscopic dose inhomogeneity, but also on the microscopic spectrum of doses stemming from the variability of energy transfer by charged particles as well as the multiple ionization events to which the target cell nucleus is exposed.

Chromosomal biodosimetry by unfolding a mixed Poisson distribution: a generalized model

Purpose : The current chromosomal biodosimetry system is practically limited to the estimation of equivalent whole-body dose in the low or moderate dose range. To circumvent this problem, a new dosimetry system was developed which was effective over a wide dose range and dose gradient. Materials and methods : In order to establish a quantitative formalism of a comprehensive dose-response kinetics, chromosome aberration frequencies were studied in human peripheral blood lymphocytes irradiated in vitro with γ-rays in a dose range of 0.01-50Gy. Using the dose-yield relationship thus established, a new model of biodosimetry was developed which involved unfolding the chromosome aberration distribution into a mixed Poisson distribution and thence into a dose-distribution profile. The model was then tested with chromosome aberration data in lymphocytes irradiated in vitro, simulated partial body irradiation, accidental radiation exposure, therapeutic local irradiation and protracted exposure by internal deposit of Thorotrast. Results : The dose-yield relations over a wide dose range fit satisfactorily a multiparametric dose-response curve, which included the first approximation kinetics of linear-quadratic dose-response and its distortion by mutual interference among multiple breaks on a chromosome arm. The unfolding strategy using these dose-response kinetics was successfully applied to the various types of radiation exposures; the reconstructed dose profile showing a sharp unimodal peak for moderate or high doses of γ-rays in vitro irradiation, broadening for high-linear energy transfer radiation, discrimination of doses in the mixed culture of irradiated and unirradiated blood, and reasonable dose distribution for the in vivo exposures. Conclusion : A novel biodosimetry system was developed. The system is innovative in that it provides information not only on the macroscopic dose inhomogeneity, but also on the microscopic spectrum of doses stemming from the variability of energy transfer by charged particles as well as the multiple ionization events to which the target cell nucleus is exposed.

Space Radiation Protection: Comparison of Effective Dose to Bone Marrow Dose Equivalent

In many instances, bone marrow dose equivalents averaged over the entire body have been used as a surrogate for whole-body dose equivalents in space radiation protection studies. However, career radiation limits for space missions are expressed as effective doses. This study compares calculations of effective doses to average bone marrow dose equivalents for several large solar particle events (SPEs) and annual galactic cosmic ray (GCR) spectra, in order to examine the suitability of substituting bone marrow dose equivalents for effective doses. Organ dose equivalents are computed for all radiosensitive organs listed in NCRP Report 116 using the BRYNTRN and HZETRN space radiation transport codes and the Computerized Anatomical Man (CAM) model. These organ dose equivalents are then weighted with the appropriate tissue weighting factors to obtain effective doses. Various thicknesses of aluminum shielding, which are representative of nominal spacecraft and SPE storm shelter configurations, are used in the analyses. For all SPE configurations, the average bone marrow dose equivalent is considerably less than the calculated effective dose. For comparisons of the GCR, there is less than a ten percent difference between the two methods. In all cases, the gonads made up the largest percentage of the effective dose.