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As hematopoietic stem and progenitor cells (HSPCs) self-renew throughout life, accumulation of genomic alterations can potentially give rise to radiation carcinogenesis. In this study we examined DNA double-strand break (DSB) induction and repair as well as mutagenic effects of ionizing radiation in CD34+ cells and T lymphocytes from the umbilical cord of newborns. The age dependence of DNA damage repair end points was investigated by comparing newborn T lymphocytes with adult peripheral blood T lymphocytes. As umbilical cord blood (UCB) contains T lymphocytes that are practically all phenotypically immature, we examined the radiation response of separated naive (CD45RA+) and memory (CD45RO+) T lymphocytes. The number of DNA DSBs was assessed by microscopic scoring of γ-H2AX/53BP1 foci 0.5 h after low-dose radiation exposure, while DNA repair was studied by scoring the number of residual γ-H2AX/53BP1 foci 24 h after exposure. Mutagenic effects were studied by the cytokinesis block micronucleus (CBMN) assay. No significant differences in the number of DNA DSBs induced by low-dose (100-200 mGy) radiation were observed among the three different cell types. However, residual γ-H2AX/53BP1 foci levels 24 h postirradiation were significantly lower in CD34+ cells compared to newborn T lymphocytes, while newborn T lymphocytes showed significantly higher foci yields than adult T lymphocytes. No significant differences in the level of radiation-induced micronuclei at 2 Gy were observed between CD34+ cells and newborn T lymphocytes. However, newborn T lymphocytes showed a significantly higher number of micronuclei compared to adult T lymphocytes. These results confirm that CD34+ cell quiescence promotes mutagenesis after exposure. Furthermore, we can conclude that newborn peripheral T lymphocytes are significantly more radiosensitive than adult peripheral T lymphocytes. Using the results from the comparative study of radiation-induced DNA damage repair end points in naive (CD45RA+) and memory (CD45RO+) T lymphocytes, we could demonstrate that the observed differences between newborn and adult T lymphocytes can be explained by the immunophenotypic change of T lymphocytes with age, which is presumably linked with the remodeling of the closed chromatin structure of naive T lymphocytes. [ABSTRACT FROM AUTHOR]

In the event of a mass casualty radiation incident, the gamma-H2AX foci assay could be a useful tool to estimate radiation doses received by individuals. The rapid processing time of blood samples of just a few hours and the potential for batch processing, enabling high throughput, make the assay ideal for early triage categorisation to separate the 'worried well' from the low and critically exposed by quantifying radiation-induced foci in peripheral blood lymphocytes. Within the RENEB framework, 8 European laboratories have taken part in the first European gamma-H2AX biodosimetry exercise, which consisted of a telescoring comparison of 200 circulated foci images taken from 8 samples, and a comparison of 10 fresh blood lymphocyte samples that were shipped overnight to participating labs 4 or 24 h post-exposure. Despite large variations between laboratories in the dose- response relationship for foci induction, the obtained results indicate that the network should be able to use the gamma-H2AX assay for rapidly identifying the most severely exposed individuals within a cohort who could then be prioritised for accurate chromosome dosimetry. [ABSTRACT FROM AUTHOR]

Objectives: Investigation of DNA damage induced by CT x-rays in paediatric patients versus patient dose in a multicentre setting.Methods: From 51 paediatric patients (median age, 3.8 years) who underwent an abdomen or chest CT examination in one of the five participating radiology departments, blood samples were taken before and shortly after the examination. DNA damage was estimated by scoring γ-H2AX foci in peripheral blood T lymphocytes. Patient-specific organ and tissue doses were calculated with a validated Monte Carlo program. Individual lifetime attributable risks (LAR) for cancer incidence and mortality were estimated according to the BEIR VII risk models.Results: Despite the low CT doses, a median increase of 0.13 γ-H2AX foci/cell was observed. Plotting the induced γ-H2AX foci versus blood dose indicated a low-dose hypersensitivity, supported also by an in vitro dose-response study. Differences in dose levels between radiology centres were reflected in differences in DNA damage. LAR of cancer mortality for the paediatric chest CT and abdomen CT cohort was 0.08 and 0.13 ‰ respectively.Conclusion: CT x-rays induce DNA damage in paediatric patients even at low doses and the level of DNA damage is reduced by application of more effective CT dose reduction techniques and paediatric protocols. . [ABSTRACT FROM AUTHOR]

Objectives: Investigation of DNA damage induced by CT x-rays in paediatric patients versus patient dose in a multicentre setting. Methods: From 51 paediatric patients (median age, 3.8 years) who underwent an abdomen or chest CT examination in one of the five participating radiology departments, blood samples were taken before and shortly after the examination. DNA damage was estimated by scoring γ-H2AX foci in peripheral blood T lymphocytes. Patient-specific organ and tissue doses were calculated with a validated Monte Carlo program. Individual lifetime attributable risks (LAR) for cancer incidence and mortality were estimated according to the BEIR VII risk models. Results: Despite the low CT doses, a median increase of 0.13 γ-H2AX foci/cell was observed. Plotting the induced γ-H2AX foci versus blood dose indicated a low-dose hypersensitivity, supported also by an in vitro dose-response study. Differences in dose levels between radiology centres were reflected in differences in DNA damage. LAR of cancer mortality for the paediatric chest CT and abdomen CT cohort was 0.08 and 0.13 ‰ respectively. Conclusion: CT x-rays induce DNA damage in paediatric patients even at low doses and the level of DNA damage is reduced by application of more effective CT dose reduction techniques and paediatric protocols. Key Points: • CT induces a small, significant number of double- strand DNA breaks in children. • More effective CT dose reduction results in less DNA damage. • Risk estimates based on the LNT hypothesis may represent underestimates. [ABSTRACT FROM AUTHOR]

Within the EU MULTIBIODOSE project, the automated micronucleus (MN) assay was optimised for population triage in large-scale radiological emergencies. For MN scoring, two approaches were applied using the Metafer4 platform (MetaSystems, Germany): fully automated scoring and semi-automated scoring with visual inspection of the gallery of MN-positive objects. Dose–response curves were established for acute and protracted whole-body and partial-body exposures. A database of background MN yields was set up, allowing determination of the dose detection threshold in both scoring modes. An analysis of the overdispersion of the MN frequency distribution σ2/µ obtained by semi-automated scoring showed that the value of this parameter represents a reliability check of the calculated equivalent total body dose in case the accident overexposure is a partial-body exposure. The elaborated methodology was validated in an accident training exercise. Overall, the semi-automated scoring procedure represents important added value to the automated MN assay. [ABSTRACT FROM AUTHOR]

In the case of a large scale radiation accident high throughput methods of biological dosimetry for population triage are needed to identify individuals requiring clinical treatment. The dicentric assay performed in web-based scoring mode may be a very suitable technique. Within the MULTIBIODOSE EU FP7 project a network is being established of 8 laboratories with expertise in dose estimations based on the dicentric assay. Here, the manual dicentric assay was tested in a web-based scoring mode. More than 23,000 high resolution images of metaphase spreads (only first mitosis) were captured by four laboratories and established as image galleries on the internet (cloud). The galleries included images of a complete dose effect curve (0-5.0 Gy) and three types of irradiation scenarios simulating acute whole body, partial body and protracted exposure. The blood samples had been irradiated in vitro with gamma rays at the University of Ghent, Belgium. Two laboratories provided image galleries from Fluorescence plus Giemsa stained slides (3 h colcemid) and the image galleries from the other two laboratories contained images from Giemsa stained preparations (24 h colcemid). Each of the 8 participating laboratories analysed 3 dose points of the dose effect curve (scoring 100 cells for each point) and 3 unknown dose points (50 cells) for each of the 3 simulated irradiation scenarios. At first all analyses were performed in a QuickScan Mode without scoring individual chromosomes, followed by conventional scoring (only complete cells, 46 centromeres). The calibration curves obtained using these two scoring methods were very similar, with no significant difference in the linear-quadratic curve coefficients. Analysis of variance showed a significant effect of dose on the yield of dicentrics, but no significant effect of the laboratories, different methods of slide preparation or different incubation times used for colcemid. The results obtained to date within the MULTIBIODOSE project by a network of 8 collaborating laboratories throughout Europe are very promising. The dicentric assay in the web based scoring mode as a high throughput scoring strategy is a useful application for biodosimetry in the case of a large scale radiation accident. [ABSTRACT FROM AUTHOR]

The focus of the study is an intercomparison of laboratories' dose-assessment performances using the cytokinesis-block micronucleus (CBMN) assay as a diagnostic triage tool for individual radiation dose assessment. Homogenously X-irradiated (240 kVp, 1 Gy/min) blood samples for establishing calibration data (0.25-5 Gy) as well as blind samples (0.1-6.4 Gy) were sent to the participants. The CBMN assay was performed according to protocols individually established and varying among participating laboratories. The time taken to report dose estimates was documented for each laboratory. Additional information concerning laboratory organization/ characteristics as well as assay performance was collected. The mean absolute difference (MAD) was calculated and radiation doses were merged into four triage categories reflecting clinical aspects to calculate accuracy, sensitivity and specificity. The earliest report time was 4 days after sample arrival. The CBMN dose estimates were reported with high accuracy (MAD values of 0.20-0.50 Gy at doses below 6.4 Gy for both manual and automated scoring procedures), but showed a limitation of the assay at the dose point of 6.4 Gy, which resulted in a clear dose underestimation in all cases. The MAD values (without 6.4 Gy) differed significantly (P=0.03) between manual (0.25 Gy, SEM=0.06, n=4) or automated scoring procedures (0.37 Gy, SEM=0.08, n=5), but lowest MAD were equal (0.2 Gy) for both scoring procedures. Likewise, both scoring procedures led to the same allocation of dose estimates to triage categories of clinical significance (about 83% accuracy and up to 100% specificity). [ABSTRACT FROM AUTHOR]

Objective The aim of this study was to repopulate decellularized heart valve matrices with ovine mesenchymal stem cells (o MSCs) by the use of platelet gel ( PG) supernatant, a storage vehicle for growth factors. Methods o MSCs were exposed to different concentrations of PG-released supernatant and cell proliferation was evaluated using the MTS assay. o MSC motility and invasiveness were assayed using a Boyden chamber. A quantitative sandwich enzyme immunoassay was used to examine amounts of b FGF and TGF-β1 in the PG supernatant. Repopulation of acellular heart valve matrices was stimulated by seeding matrices with o MSCs supplemented with the PG supernatant. Results The most significant increase in proliferation induced by PG supernatant appeared at 1 × 105 plts/ml concentration. Higher concentrations evoked reduction of the stimulatory process. o MSC motility was most significantly stimulated at 1 × 106 plts/ml. Stimulating invasiveness of o MSCs needed the much higher concentration of 2 × 106 plts/ml. Immunoassays revealed that sheep PG supernatant contains 184.8 pg/ml b FGF and 60.5 ng/ml TGF-β1. Moreover, repopulation of acellular heart valve matrices was significantly enhanced by PG supernatant addition and resulted in upregulation of the myofibroblast marker alpha-smooth muscle actin. Conclusions Growth factors released from platelets had the potential to induce cell repopulation in a heart valve tissue engineering procedure, through stimulation of mesenchymal stem-cell migration and invasion. [ABSTRACT FROM AUTHOR]

The aim of this investigation was to study the influence of genetic polymorphisms of biotransformation enzymes and dopamine receptors on neurobehavioral effects in referents ( n = 53), solvent-workers ( n = 144), and chronic toxic encephalopathy (CTE) patients ( n = 33). All participants were interviewed for exposure data and confounding factors and underwent a clinical examination. Neurobehavioral complaints (neurotoxicity symptom checklist-60) and effects [simple reaction time (SRT), symbol digit substitution (SDS), hand–eye coordination (HEC), and digit span backwards (DSB)] were evaluated with a computer assisted test battery. The following genotypes were determined: GSTM1, GSTT1, GSTP1, DRD2 Taq1A, DRD2 Taq1B, and DRD2-141Cdel. Neurotoxic effects and complaints were significantly higher in CTE patients and were related to both duration and level of exposure. An equal distribution of genotypes was found between all groups. Logistic regression analysis revealed that GSTT1 was negatively associated with sleep and sensorimotor complaints. GSTM1 had a protecting influence on the relationship between logDSB and the cumulative exposure index and between logSRT and cumulative exposure index and degree of exposure, respectively. This effect was also found when correcting for age, education level, alcohol consumption, and smoking. DRD2-141Cdel polymorphisms had a negative influence on the relationship between logSDS and the total exposure time. GSTT1 might be protective against sleep and sensorimotor complaints, whereas GSTM1 seems to decrease sustained attention and short-term memory problems in relation to solvent exposure. Individuals possessing DRD2-141Cdel variant experienced more visuomotor problems. [ABSTRACT FROM AUTHOR]

Using a single colour fluorescence in situ hybridisation technique, dose-responses were derived for a range of chromosomally aberrant cell types and categories of aberrations induced in peripheral blood lymphocytes by alpha-particle radiation and analysed in their first in vitro division. For a range of doses that resulted predominantly in targeted cells receiving a single hit, i.e. 0-200 mGy, linear models fitted all the different categories of aberrant cells and aberration types but the profile of chromosome damage differed for 500 mGy, reflecting the effect of different track structure. [ABSTRACT FROM AUTHOR]

For 318 patients in 8 different Belgian hospitals, the entire skin-dose distribution was mapped using a grid of 70 thermoluminescence dosemeters per patient, allowing an accurate determination of the maximum skin dose (MSD). Dose- area product (DAP) values, exposure parameters and geometry, together with procedure, patient and cardiologist characteristics, were also registered. Procedures were divided into two groups: diagnostic procedures (coronary angiography) and therapeutic procedures (dilatation, stent, combined procedures (e.g. coronary angiography + dilatation + stent)). The mean value of the MSD was 0.310 Gy for diagnostic and 0.699 Gy for therapeutic procedures. The most critical projection for receiving the MSD is the LAO90 (left anterior oblique) geometry. In 3% of cases, the MSD exceeded the 2 Gy dose threshold for deterministic effects. Action levels in terms of DAP values as the basis for a strategy for follow-up of patients for deterministic radiation skin effects were derived from measured MSD and cumulative DAP values. Two DAP action levels are proposed. A first DAP action level of 125 Gy cm² corresponding to the dose threshold of 2 Gy would imply an optional radiopathological follow-up depending on the cardiologist's decision. A second DAP action level of 250 Gy cm² corresponding to the 3 Gy skin dose would imply a systematic follow-up. Dose reference levels — 71.3 Gy cm² for diagnostic and 106.0 Gy cm² for therapeutic procedures — were derived from the 75 percentile of the DAP distributions. As a conclusion, we propose that total DAP is registered in patient's record file, as it can serve to improve the follow-up of patients for radiation-induced skin injuries. [ABSTRACT FROM AUTHOR]

The association between chromosomal radiosensitivity and genetic predisposition to head and neck cancer was investigated in this study. In all, 101 head and neck cancer patients and 75 healthy control individuals were included in the study. The G(2) assay was used to measure chromosomal radiosensitivity. The results demonstrated that head and neck cancer patients had a statistically higher number of radiation-induced chromatid breaks than controls, with mean values of 1.23 and 1.10 breaks per cell, respectively (P<0.001). Using the 90th percentile of the G(2) scores of the healthy individuals as a cutoff value for chromosomal radiosensitivity, 26% of the cancer patients were radiosensitive compared with 9% of the healthy controls (P=0.008). The mean number of radiation-induced chromatid breaks and the proportion of radiosensitive individuals were highest for oral cavity cancer patients (1.26 breaks per cell, 38%) and pharynx cancer patients (1.27 breaks per cell, 35%). The difference between patients and controls was most pronounced in the lower age group (

Effective dose (E), representing the risk of late radiation-induced effects, can be estimated by the use of conversion factors (CF), converting direct measurable quantities such as dose-area-product into E. Eight Belgian hospitals participated in the study with a total number of 318 procedures. E-values, calculated with PCXMC, were compared for the different hospitals for diagnostic and therapeutic procedures separately. E-values varied significantly depending on the hospital where the procedure was performed (P <0.001), on filtration insertion (P <0.001), on whether a centre is a training centre or not, the dose conscious action of the cardiologists and the complexity of the procedure (P <0.001). Hospital-specific CF were calculated. An average CF of 0.185 mSv Gycm-2 was obtained with a satisfactory correlation (r = 0.966, P < 0.001). The differences in CF between hospitals were due to, a large extent, the availability of additional filtration in cinegraphy mode (P <0.001) and not to the differences in irradiation geometries in the clinical protocol of the interventional procedures. [ABSTRACT FROM AUTHOR]

In this paper, a large-scale multicentre patient dose study performed in eight Belgian interventional cardiology departments is presented. Effective dose (E) was calculated based on a detailed dose--area product (DAP)-registration during each procedure and by using conversion coefficients generated by the Monte Carlo-based computer program PCXMC. Conversion coefficients were found to be 0.177 mSv Gycm-2 for systems that do not use any additional copper filtration in cineradiography and 0.207 mSv Gycm-2 for systems that use additional copper filtration in cineradiography. Mean E values of 9.6 and 15.3 mSv for diagnostic and therapeutic procedures, respectively, were obtained. DAP distributions were investigated in order to derive dose reference levels: 71 and 106 Gycm² for diagnostic and therapeutic procedures, respectively, are proposed. Significant differences were observed in DAP distributions taking into account whether additional copper filtration was used in the cineradiography mode. Apart from the skin, the organs most at risk are lungs and heart. The probability of fatal cancer for the studied population amounted to 1.1 x 10-4 and 2.1 x 10-4 for diagnostic and therapeutic procedures, respectively, for the age distribution of the patients considered in this multicentre study. [ABSTRACT FROM AUTHOR]

An evaluation of the image quality of an amorphous silicon fiat-panel detector system and a computed radiology system compared with a screen-film system was performed by means of contrast-detail phantom images. Hard and soft copy images were evaluated. Although patient dose at clinical settings was strongly decreased with the amorphous silicon system, the low-contrast visibility with this system was still significantly better than with the screen-film system. For the computed radiology system, low-contrast visibility was comparable to the screen-film system. Best results were obtained by soft copy reading at full resolution with adaptation of contrast and brightness. Changing tube voltage (102–133 kV), or additional filtration, did not significantly affect image quality. However, low-contrast visibility improved significantly with increasing exposure. It was clearly demonstrated that, in chest imaging, the amorphous silicon system has superior imaging characteristics compared to the screen-film and the computed radiology system. [ABSTRACT FROM AUTHOR]

Purpose. The aim of this study was twofold: firstly, to determine whether the European Association of Nuclear Medicine (EANM) dosage card results in weight-independent effective doses or weight-independent count rates; secondly, to deter-mine whether one dosage card is sufficient for 95 different radiopharmaceuticals, and, if not, how many cards we reasonably need to take into account inter-tracer variability. Methods. Normalisation factors for count rate and effective dose were calculated as a function of body weight, with 70 kg as standard. Calculations were performed, using whole-body absorption fractions and MIRDOSE 3 software, for seven anthropomorphic phantoms and ten radionuclides. An analytic function for both relations was proposed. Normalisation factors for effective dose for 95 radiophar-maceuticals were investigated using cluster analysis. Results. Normalisation factors for count rate and effective dose can be estimated accurately as a function of body weight W by (W/70)a holding only one parameter, called the a value. The a values for 95 radiopharmaceuticals were classified into three clusters (nA = 7, nB = 76, nC = 12). Cluster A contains tracers for renal studies. Cluster B contains all remaining tracers, except iodinelabelled tracers for thyroid studies and 89Sr for therapy, which belong to cluster C. Conclusion. Correction factors proposed by the EANM task group mainly correct for effective dose. They are very similar to the factors obtained for cluster A. Using the EANM factors for tracers belonging to clusters B and C results in significantly higher effective doses to children. We suggest using three tracer-dependent dosage cards for which the correction factors have been calculated to obtain weight-independent effective doses. [ABSTRACT FROM AUTHOR]

A technician involved in the maintenance of X-ray equipment visited the occupational medicine service with complaints of skin lesions, apparently caused by an accidental exposure three months earlier. To estimate the dose received by the technician in the accident, biodosimetry was performed 6 and 18 months post-exposure with the dicentric and micronucleus assays. Part of the latest blood sample was also used for retrospective dosimetry by fluorescence in situ hybridisation (FISH) analysis for translocations. The data obtained 6 and 18 months post-exposure indicate that both dicentrics and micronuclei disappear with a half-time of 1 y. After correction for delayed blood sampling, dose values of 0.75 Gy (95% confidence limits 0.56-1.05 Gy) from dicentrics and 0.96 Gy (95% confidence limits 0.79-1.18 Gy) from micronuclei were obtained. FISH analysis of translocations resulted in a dose estimate of 0.79 Gy (95% confidence limits 0.61-0.99 Gy). The satisfactory agreement between the three cytogenetic endpoints supports the use of the micronucleus assay for triage purposes in the case of large scale radiological accidents and provides further evidence for the valid use of FISH for translocations as a reliable retrospective biological dosimeter. [ABSTRACT FROM AUTHOR]

Purpose: The chromosomal radiosensitivity of a selected group of familial breast cancer patients carrying a mutation in BRCAI (n = 11) or BRCA2 (n=9) and a group of healthy mutation carriers (n = 12) was investigated and compared to a reference group of breast cancer patients without a BRCA1/2 mutation (n = 78) and a group of healthy women carrying no mutation (n = 58), Materials and methods: The chromosomal radiosensitivity was assessed with the G2 and the G0-micronucleus (MN)-assay on fresh blood samples and on Epstein-Barr virus (EBV)-transformed lymphoblastoid cell lines. For the MN-assay, lymphocytes were exposed in vitro to 3.5Gy and 2Gy 60Co γ-rays at a high dose rate (HDR) or low dose rate (LDR), 70-h post-irradiation cultures were arrested and micronuclei were scored in 1000 binucleate cells. For the G2-assay lymphocytes were irradiated in vitro with a dose of 0.4Gy 60Co γ-rays after 71h incubation. Cultures were arrested 90 min after irradiation and chromatid breaks were scored in 50 metaphases Results. The group of breast cancer patients with it BRCAI or 2 mutation was on average more radiosensitive than the control group, but not different from breast cancer patients without a BRCA mutation. The radiation response of healthy BRCA1/2 carriers was not significantly different from the control group and also not different from relatives without a BRCA mutation. Comparing the radiation response in EBV cell lines derived from breast cancer patients with or without a BRCAI mutation revealed no significant difference. Conclusions: Our results reveal that chromosomal radiosensitivity observed in breast cancer patients heterozygous for BRCAI or 2 mutations, could not be demonstrated in healthy BRCA1/2 mutation carriers. This suggests that mutations in BRCAI or 2 genes are not playing a main role hi chromosomal radiosensitivity, this although BRCAI and 2 are both involved in DNA repair/signalling processes. [ABSTRACT FROM AUTHOR]

To investigate the chromosomal radiosensitivity of lymphocytes in cancer patients the micronucleus (MN) assay is often used and performed on freshly drawn peripheral blood lymphocytes. The use of Epstein–Barr virus (EBV)‐transformed lymphoblastoid cell lines may have a lot of advantages (e.g. large pool of cells) compared with fresh blood samples. In this study we have investigated whether the response of EBV‐transformed lymphoblastoid cell lines to irradiation in the G1/S/G2 phases of the cell cycle is the same as in concordant whole blood cultures where primary lymphocytes were irradiated in the G0 phase of the cell cycle. For this study the MN assay (2 Gy) was performed on EBV‐transformed cell lines of breast cancer patients and a group of healthy women. Those breast cancer patients were selected who showed an elevated chromosomal radiosensitivity in fresh blood samples in a previous study. The results demonstrated that the enhanced chromosomal radiosensitivity observed in fresh blood cultures of breast cancer patients is not present in EBV‐transformed cell lines derived from the same blood samples. Therefore, care must be taken when EBV cell lines are used to assess chromosomal radiosensitivity in breast cancer patients. [ABSTRACT FROM AUTHOR]

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The bony repair effect of different Calcium Phosphate Bone Cements was tested in a dog model. Seven different formulations were synthesized and tested on their biocompatibility, osseoconduction and biodegradability. Three dogs were used in this pilot study, in each dog 4 cranial, circular defects were made with a critical size diameter of 12 mm. Autologous bone was used as a control. The dogs were sacrificed after 6 months. Mineral phase analysis showed a reaction of the cements to form a more or less crystalline calciumhydroxyapatite. Histologic evaluation revealed that the presence of the cements stimulated the formation of a thin bone layer on the cranial and caudal side of each defect. The cements did not evoke an inflammatory reaction. Two formulations showed extensive bone formation. [ABSTRACT FROM AUTHOR]

The chromosomal radiosensitivity of breast cancer patients with a known or putative genetic predisposition was investigated and compared to a group of healthy women. The chromosomal radiosensitivity was assessed with the G2 and the G0-micronucleus assay. For the G2 assay lymphocytes were irradiated in vitro with a dose of 0.4 Gy (60)Co gamma-rays after 71 h incubation, and chromatid breaks were scored in 50 metaphases. For the micronucleus assay lymphocytes were exposed in vitro to 3.5 Gy (60)Co gamma-rays at a high dose rate or low dose rate. 70 h post-irradiation cultures were arrested and micronuclei were scored in 1000 binucleate cells. The results demonstrated that the group of breast cancer patients with a known or putative genetic predisposition was on the average more radiosensitive than a population of healthy women, and this with the G2 as well as with the high dose rate and low dose rate micronucleus assay. With the G2 assay 43% of the patients were found to be radiosensitive. A higher proportion of the patients were radiosensitive with the micronucleus assay (45% with high dose rate and 61% with low dose rate). No correlation was found between the G2 and the G0-micronucleus chromosomal radiosensitivity. Out of the different subgroups considered, the group of the young breast cancer patients without family history showed the highest percentage of radiosensitive cases in the G2 (50%) as well as in the micronucleus assay (75-78%). [ABSTRACT FROM AUTHOR]

Purpose: To study chromosomal radiosensitivity in a population of radiation workers and investigate the possibility of an adaptive response in lymphocytes of workers after short-term occupational exposure to ionizing radiation. Materials and methods: The studied group comprised 41 workers temporarily employed at the Nuclear Power Plant Doel (Belgium) for reactor maintenance. A blood sample was taken before and directly after the exposure period of about 1 month. Chromosomal radiosensitivity was assessed in vitro by the G2 assay and the G0 micronucleus (MN) assay. For the MN assay, a low dose-rate (LDR) in vitro irradiation protocol was applied in addition to high dose-rate (HDR) irradiation of the blood samples in order to determine the dose-rate sparing (DRS) effect. Results: No statistically significant effect of the occupational exposures (up to 10 mSv) on the baseline MN frequencies without in vitro irradiation was observed. A comparison of the number of chromatid aberrations pre- and post-exposure shows no effect of the occupational exposure. On the other hand, the G0-MN assay with the LDR irradiation protocol reveals a systematic reduction in chromosomal radiosensitivity by the exposure, increasing with dose. For workers who received the highest dose (4-10 mSv) a statistically significant (p < 0.05) decrease of the in vitro induced MN yields and increase of the dose-rate sparing was observed. Conclusions: Short-term low-dose occupational exposure may act as an in vivo adaptive dose and stimulate repair in G0 lymphocytes. [ABSTRACT FROM AUTHOR]

In radionuclide therapy with iodine-131 labelled pharmaceuticals, free [sup 131] I may be released and trapped by the thyroid, causing an undesirable radiation burden. To prevent this, stable iodide such as potassium iodide (KI) can be given to saturate the thyroid before [sup 131] I is administered. The guidelines of the European Association of Nuclear Medicine do not, however, recommend special precautions when administering [sup 131] I-lipiodol therapy for hepatocellular carcinoma. Nevertheless, some authors have reported [sup 131] I uptake in the thyroid as a consequence of such therapy. In this study, the influence of prophylactic KI on the thyroid uptake and dose (MIRD dosimetry) was prospectively investigated. [sup 131] I-lipiodol was given as a slow bolus selectively in the proper hepatic artery or hyperselectively in the right and/or left hepatic artery. Patients were prospectively randomised into two groups. One group received KI in a dose of 100 mg per day starting 2 days before [sup 131] I-lipiodol administration and continuing until 2 weeks after therapy (KI group; n=31), while the other group received no KI (non-KI group; n=37). Thyroid uptake was measured scintigraphically as a percentage of administered activity 7 days after [sup 131] I-lipiodol (n=68 treatments). The absorbed radiation dose to the thyroid was assessed by scintigraphy after 7 and 14 days using a mono-exponential fitting model and MIRD dosimetry (n=40 treatments). The mean activity of [sup 131] I-lipiodol administered was 1,835 MBq in a volume of 2 (n=17) or 4 (n=51) ml. Thyroid uptake was lower in the KI group, being 0.23%±0.06% of injected activity (n=31) compared with 0.42%±0.20% in the non-KI group (n=37); the mean thyroid dose was 5.5±1.6 Gy in the KI group (n=19) versus 11.9±5.9 Gy in the non-KI group (n=21). These differences were statistically significant (P<0.001). No effect of the amount of added cold lipiodol (4 vs 2 ml total volume) or selectivity... [ABSTRACT FROM AUTHOR]

Purpose: To determine by means of the G2 assay the number of chromatid breaks induced by low-LET γ-rays and high-LET neutrons, and to compare the kinetics of chromatid break rejoining for radiations of different quality. Materials and methods: The G2 assay was performed on blood samples of four healthy donors who were irradiated with low-LET γ-rays and high-LET neutrons. In a first set of experiments a dose-response curve for the formation of chromatid breaks was carried out for γ-rays and neutrons with doses ranging between 0.1 and 0.5 Gy. In a second set of experiments, the kinetics of chromatid break formation and disappearance were investigated after a dose of 0.5 Gy using post-irradiation times ranging between 0.5 and 3.5 h. For the highest dose of 0.5 Gy, the number of isochromatid breaks was also scored. Results: No significant differences in the number of chromatid breaks were observed between low-LET γ-rays and high-LET neutrons for the four donors at any of the doses given. The dose-response curves for the formation of chromatid breaks are linear for both radiation qualities and RBEs = 1 were obtained. Scoring of isochromatid breaks at the highest dose of 0.5 Gy revealed that high-LET neutrons were, however, more effective at inducing isochromatid breaks (RBE = 6.2). The rejoining experiments further showed that the kinetics of disappearance of chromatid breaks following irradiation with low-LET γ-rays or high-LET neutrons were not significantly different. Half-times of 0.92 h for γ-rays and 0.84 h for neutrons were obtained. Conclusions: Applying the G2 assay, the results demonstrate that at low doses of irradiation, the induction as well as the disappearance of chromatid breaks is independent of the LET of the radiation qualities used (0.24 keV μm[sup -1 60]Co γ-rays and 20 keV μm[sup -1] fast neutrons). As these radiation qualities produce the same initial number of double-strand breaks, the results support the signal model that proposes that chromatid breaks are the result of an exchange process which is triggered by a single double-strand break. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the incidence of translocations induced by iodine-131 therapy in thyrotoxicosis patients 1 year after the administration of the radiolabelled compound. Materials and methods: Tricolour FISH with whole-chromosome-specific probes for chromosomes 2, 4 and 8 was used for scoring translocations. From the genomic translocation frequencies, derived using the Lucas formula, equivalent whole-body doses were calculated, based on the in vitro [sup 60]Co γ-ray dose-response curve. Results: A total of 101 translocations were observed in 4864 metaphases, 63% being of the two-way type. In the control group used for obtaining dose-response data, nine translocations were observed in 5278 metaphases, 55% being two-way translocations. No correlation was found between the observed frequency of translocations and administered radioactivity. Using the in vitro dose-response, an estimated average dose for the group of nine patients of 0.79±0.22Gy was obtained. Compared with frequencies following the assumption that the involvement of a particular chromosome in a two-break exchange-type aberration is proportional to its DNA content, chromosome 4 was more frequently involved and chromosomes 2 and 8 less frequently involved in chromosomal rearrangements. Conclusion: This study shows that [sup 131]I therapy for thyrotoxicosis patients induced translocations, especially in chromosome 4, which could be detected 1 year after the administration of the radiolabelled compound. [ABSTRACT FROM AUTHOR]

Purpose: To elaborate the B-cell micronucleus (MN) response in the low-dose region in detail and to investigate the postulated deficiency in DNA-PK in B-cells. Materials and methods: Lymphocytes of five healthy volunteers were irradiated with low LET γ-rays and high LET fast neutrons with doses ranging between 0.01 and 2 Gy. After post-irradiation incubation, B- and T-cells were isolated via CD3 and CD19 immunomagnetic microbeads. MN were analysed in both subpopulations. To study the underlying mechanism of chromosomal radiosensitivity, cell extracts prepared from purified B- and T-cells were subjected to SDS-electrophoresis and electroblotting using antibodies directed against the DNA-PK repair enzymes Ku70/86 and DNA-PKcs. Activity measurements were performed using the SignaTECT DNA-dependent protein kinase assay. DNA double-strand break (DSB) induction and rejoining was determined using constant-field gel electrophoresis. Results: For low LET γ-rays a higher MN yield was observed in B-cells than in T-cells, but only in those samples exposed to doses < 1Gy. For 1 Gy, the MN yields were comparable and for 2 Gy even lower in B-cells compared with T-cells. After high LET neutron irradiation no significant differences in MN yields were observed between both subsets. The results of the DNA-PK experiments demonstrate that there is no difference between T- and B-cells in the basal expression and activity of DNA-PK repair proteins. No differences in DNA DSB induction and rejoining were found between T- and B-cells using constant-field gel electrophoresis. Conclusions: From the results, it was concluded that the enhanced chromosomal radiosensitivity in B-cells is restricted to low doses (<1 Gy) of low LET radiation and that the chromosomal behaviour of B-cells to low LET radiation cannot be attributed to aberrant forms of the DNA-PK components. A type of chromosomal induced radioresistance (IRR) may be a possible explanation for the observed effect. [ABSTRACT FROM AUTHOR]

A cytogenetic study was performed in lymphocytes of hospital workers occupationally exposed to X- and γ-rays using the micronucleus centromere assay. A comparison of the data for the exposed group and an age-matched group of non-exposed hospital workers showed a significant (P < 0.05) increase in centromere-positive micronuclei for the radiation workers, while no effect on centromere-negative micronuclei was present. The observed systematic increase in micronucleus frequency with age was mainly due to increased chromosome loss, reflected in the centromere-positivity of the micronuclei. The micronucleus frequencies were 40% higher in females than in males, which can again be attributed to higher chromosome loss. Two exposed individuals showed exceptionally high micronucleus yields, 90% of which were centromere-positive. In situ hybridization with a centromeric probe for chromosome X shows that X chromosome loss is responsible for these high micronucleus yields. In the studied population, smoking had no significant effect on the micronucleus yields. The results obtained indicate that in contrast to the predominantly clastogenic action of acute exposure to ionizing radiation, the aneugenic properties of radiation may be important after long-term chronic low dose exposure. [ABSTRACT FROM PUBLISHER]

Purpose: To investigate the changes in peripheral blood lymphocyte subpopulations in patients undergoing radiotherapy. Materials and methods: In 8 patients undergoing external beam radiotherapy to the pelvis, the different lymphocyte subpopulations were followed during treatment. The lymphocyte populations were determined using two-colour flow cytometry. The study comprises the T-helper, T-suppressor/cytotoxic cells, the B-lymphocytes and natural killer (NK) cells. Results: The B-cells were characterized by a steep decrease at the beginning of the radiotherapy. They reached their lowest level at an equivalent total body dose of 1.5Gy and remained constant during the rest of the therapy (10% of the initial level). In T-cells (both T-helper and T-suppressor subsets) the steep decrease was less pronounced. T-lymphocytes reached a base level at 2.5Gy equivalent total body dose (20% of the initial level). No significant differences between the T-helper and the T-suppressor/cytotoxic cells were observed. NK cells were characterized by a weak decline during the first weeks of therapy, being less pronounced than in the other populations. Near the end of therapy, the NK cells reached the level of the T-lymphocytes. Conclusion: In vivo, NK cells were the most radioresistant and B-cells the most radiosensitive lymphocytes. No significant differences between T-helper and T-suppressor/cytotoxic cells were observed. These data are in agreement with the differences in apoptosis induction in peripheral blood lymphocyte subpopulations after in vitro gamma-irradiation of whole blood lymphocytes. [ABSTRACT FROM AUTHOR]

Purpose: The evaluation of different cytogenetic endpoints of radiation damage for the biomonitoring of contract workers temporarily employed at nuclear power plants. Materials and methods: Blood samples from six donors were irradiated in vitro with doses ranging from 0.1 to 2Gy 60Co gamma -rays. Compared were a conventional analysis for dicentrics, the conventional micronucleus (MN) assay, the centromere micronucleus assay using p82H and an alpha AllCen pancentromeric probe, and tricolour FISH with chromosome 2, 4 and 8 DNA probes for the scoring of translocations. Results: Agreement in the number of MN between Giemsa-and propidium iodine fluorescence-stained preparations was obtained. The control samples showed higher centromere positivity for the MN after FISH with the p82H probe compared with the alpha AllCen probe. The MN results with both probes showed a slight but systematic increase in the number of centromerepositive MN with dose, indicating that radiation, although principally clastogenic, also has aneuploidogenic properties. The values of the genomic translocation frequency (FG) derived from the observed translocation frequencies were systematically higher than the dicentric yields. Comparing the sensitivity of the di erent methods with restriction of the scoring time to 1 day for biomonitoring purposes, the centromere micronucleus assay had the lowest dose detection limit (0.1 to 0.2Gy). Conclusion: This study shows that at present only the centromere micronucleus assay can combine high sensitivity with a reasonable scoring time for the biomonitoring of relatively large populations. [ABSTRACT FROM AUTHOR]

This study reports on the distribution and radiation dosimetry of iodine-123 labelled trans- Z-iodomethyl- N, N-diethyltamoxifen (123-ITX), a promising radioligand for prediction of the therapeutic efficacy of unlabelled tamoxifen in human breast carcinoma. Whole-body scans were performed up to 24 h after intravenous injection of 123-ITX (mean: 146 MBq, range: 142–148 MBq) in five female volunteers, four with and one without thyroid blockade. Blood samples were taken at various times up to 24 h after injection. Urine was also collected up to 24 h after injection, allowing calculation of renal clearance and interpretation of whole-body clearance. Time-activity curves were generated for the thyroid, heart, brain, breasts, liver and gallbladder by fitting the organ-specific geometric mean counts, obtained from regions of interest. The MIRD formulation was applied to calculate the absorbed radiation doses for various organs. The images showed rapid hepatobiliary excretion, resulting in good imaging conditions for the thoracic region, whereas imaging of the abdominal region was impeded by extensive bowel activity. The breast to non-specific uptake ratio increased over time. 123-ITX was cleared by both the kidneys and the gastrointestinal tract. At 50 h p.i. the mean excretion in the urine was 89.4% (SD 5.7%). If the thyroid was not blocked, it was one of the critical organs. The highest absorbed doses were received by the excretory organs, i.e. the urinary bladder wall, the lower and upper large intestine, and the gallbladder wall. The average effective dose of 123-ITX was estimated to be 0.0084 mSv/MBq. The amount of 123-ITX required for adequate imaging of tumoral uptake results in an acceptable effective dose to the patient. [ABSTRACT FROM AUTHOR]

Resting lymphocytes are sensitive to radiation damage and die by apoptosis. We investigated the effect of caspase-inhibitors on radiation induced apoptosis in human peripheral blood lymphocytes. Lymphocytes were irradiated in vitro with 5 Gy 60 Co-γ-rays and cultured for 24 hours in the presence or absence of the caspase-inhibitors zVAD-fmk and zDEVD-fmk. Cell death was evaluated by electron microscopy. Irradiation in the absence of the inhibitors resulted in about 30% dead cells, almost all showing typical apoptotic morphologies. Addition of either one of the inhibitors could not rescue cells from death. Part of the dead lymphocytes (about 65%) still showed typical nuclear characteristics of apoptotic cells: sharply marginated, condensed chromatin, clumped into one sphere or into a crescent shaped mass. The remaining part of the dead cells had ultrastructural characteristics, aberrant from apoptic cells: clumping of the chromatin was less pronounced and less sharply marginated. Irregular clumps were formed. Data indicate that part of the lymphocytes go in apoptosis in a caspase-independent way. The other part shows caspase-dependent apoptosis with respect to the nuclear events. [ABSTRACT FROM AUTHOR]