Distribution of the relative biological effectiveness of fast neutrons according to the depth of the irradiated tissue

A study was made of the dependence of relative biological effectiveness (RBE) and isoeffective dose of fast neutrons (produced by U-120 cyclotron) upon the depth of the exposed tissue. It was shown that the isoeffective dose and RBE vary significantly with the depth of the tissue-equivalent medium. The investigations were carried out with the purpose of improving the radiobiological and dosimetric techniques for the treatment of malignant tumors using a neutron beam from U-120 cyclotron.     

Calculation of dose components in head phantom for boron neutron capture therapy.

Application of neutrons to cancer treatment has been a subject of considerable clinical and research interest since the discovery of the neutron by Chadwick in 1932 (3). Boron neutron capture therapy (BNCT) is a technique of radiation oncology which is used in treating brain cancer (glioblastoma multiform) or melanoma and that consists of preferentially loading a compound containing 10B into the tumor location, followed by the irradiation of the patient with a beam of neutron. Dose distribution for BNCT is mainly based on Monte Carlo simulations. In this work, the absorbed dose spatial distribution resultant from an idealized neutron beam incident upon ahead phantom is investigated using the Monte Carlo N-particles code, MCNP 4B. The phantom model used is based on the geometry of a circular cylinder on which sits an elliptical cylinder capped by half an ellipsoid representing the neck and head, both filled with tissue-equivalent material. The neutron flux and the contribution of individual absorbed dose components, as a function of depths and of radial distance from the beam axis (dose profiles) in phantom model, is presented and discussed. For the studied beam the maximum thermal neutron flux is at a depth of 2 cm and the maximum gamma dose at a depth of 4 cm.     

Chromosome aberrations in the blood lymphocytes of astronauts after space flight.

Cytogenetic analysis of the lymphocytes of astronauts provides a direct measurement of space radiation damage in vivo, which takes into account individual radiosensitivity and considers the influence of microgravity and other stress conditions. Chromosome exchanges were measured in the blood lymphocytes of eight crew members after their respective space missions, using fluorescence in situ hybridization (FISH) with chromosome painting probes. Significant increases in aberrations were observed after the long-duration missions. The in vivo dose was derived from the frequencies of translocations and total exchanges using calibration curves determined before flight, and the RBE was estimated by comparison with individually measured physical absorbed doses. The values for average RBE were compared to the average quality factor (Q) from direct measurements of the lineal energy spectra using a tissue-equivalent proportional counter (TEPC) and radiation transport codes. The ratio of aberrations identified as complex was slightly higher after flight, which is thought to be an indication of exposure to high-LET radiation. To determine whether the frequency of complex aberrations measured in metaphase spreads after exposure to high-LET radiation was influenced by a cell cycle delay, chromosome damage was analyzed in prematurely condensed chromosome samples collected from two crew members before and after a short-duration mission. The frequency of complex exchanges after flight was higher in prematurely condensed chromosomes than in metaphase cells for one crew member.     

Microdosimetry for boron neutron capture therapy.

Preclinical studies for boron neutron capture therapy (BNCT) using epithermal neutrons are ongoing at several laboratories. The absorbed dose in tumor cells is a function of the thermal neutron flux at depth, the microscopic boron concentration, and the size of the cell. Dosimetry is therefore complicated by the admixture of thermal, epithermal, and fast neutrons, plus gamma rays, and the array of secondary high-linear-energy-transfer particles produced within the patient from neutron interactions. Microdosimetry can be a viable technique for determining absorbed dose and radiation quality. A 2.5-cm-diameter tissue-equivalent gas proportional counter has been built with 50 parts per million (ppm) 10B incorporated into the walls and counting gas to simulate the boron uptake anticipated in tumors. Measurements of lineal energy (y) spectra for BNCT in simulated volumes of 1-10 microns diameter show a dose enhancement factor of 4.3 for 30 ppm boron, and a "y" of 250 keV/microns for the boron capture process. Chamber design plus details of experimental and calculated linear energy spectra will be presented.     

Chromosome aberrations induced in human lymphocytes by radiation from 252Cf.

In vitro dose--response curves of unstable chromosome aberrations in human lymphocytes have been obtained for 252Cf neutron radiation. The aberration yields fitted best to the linear function Y=aD, which is consistent with the single-track model of aberration formation for high LET radiation. The curves have been compared with others previously produced in this laboratory for several energies of neutrons and for 60Co gamma radiation. The r.b.e. for 252Cf with respect to 60Co is 27 at very low doses, decreasing to 6 at an aberration yield equivalent to 400 rad of 18 rad/hour gamma radiation. A profile of chromosome-aberration induction with depth in a perspex phantom was obtained by placing blood samples at several distances over the range 0.65-2.0 cm from the californium source. This profile was compared with depth-damage calculations for a radium needle. The r.b.e. of 252Cf radiation relative to 226Ra gamma radiation increased with the distance from the source, implying that californium is more effective at greater distances in destroying the ability of cells to divide, which may be an advantage in the treatment of large tumours.     

Comparative in vivo and in vitro study of the cytogenetic effects of 153Sm-EDTMP in lymphocytes of patients with bone metastases.

153Sm-EDTMP is a radiopharmaceutical used in nuclear medicine for relief of metastatic bone pain with promising results, but there are few studies about the effects of 153Sm-EDTMP in human cells. This study was conducted for the evaluation of the cytogenetic effects of 153Sm-EDTMP in blood lymphocytes from patients with bone metastases (without previous radio or chemotherapy), using the chromosome aberration technique. The degree of cytological damage found in in vivo blood cells of patients was compared with those found in in vitro in an adjusted dose-response curve. Blood samples were collected before and 1 hr after the administration of 153Sm-EDTMP(about 42.31 MBq/kg). The frequency of structural chromosome aberration per cell observed in 1 hr samples (0.054+/-0.035 CA/cell) was higher than basal ones (0.031+/-0.026 CA/cell), although this difference was not statistically significant (p= 0.101). For in vitro assay, blood samples were exposed to different concentrations of 153Sm-EDTMP, during 1 hr (0.37-1.11 MBq/ml). An increase in the frequency of chromosome aberration per cell as a function of the radioactive concentration was found. The data were adjusted by linear regression model (Y= 3.52+/-2.24 x 10(-2) + 11.15+/-3.46 x 10(-2) X). The frequency of aberration/cell found in vivo was 0.054 and for the same activity in vitro was 0.098, this difference being statistically significant (p = 0.02). This result may be related to blood clearance, osteoblastic activity and individual variability. For a more accurate analysis, the study of more donors is necessary.     

Absorbed doses in tissue-equivalent spheres above radioactive sources in soil

Doses due to external exposure of terrestrial biota are assessed using differential air kerma from radioactive sources in soil and energy-dependent ‘absorbed dose-per-air kerma’ conversion factors computed for spherical tissue-equivalent bodies. The presented approach allows computing average whole body absorbed dose for terrestrial organisms with body masses from 1 mg to 1,000 kg located at heights from 10 cm to 500 m above ground. Radioactive sources in soil emitting photons with energies from 10 keV to 10 MeV have been considered. Interpolation of the computed quantities over source energy, body mass, and height above ground results in plausible estimates of whole body average absorbed doses for non-human terrestrial biota from gamma-radiation emitted by any radionuclides in contaminated terrain.     

Effect of oxygen tension on chromosomal aberrations in Fanconi anaemia

Blood samples from four healthy individuals and from seven Fanconi anaemia (FA) patients were cultured at oxygen tensions ranging from 3% to 45% O2. Cultures were harvested at 72 h and scored for chromosomal aberrations. In the majority of FA patients the aberration frequency showed a tendency to increase as a function of oxygen tension over the culture, whereas the aberration frequency in healthy individuals was not affected. However, the response in FA cultures was variable among patients and in individual cases when assayed on different occasions. A much stronger effect of oxygen tension was observed when the FA blood samples had been treated with mitomycin C (0.25 microgram/ml, 30 min) before culture initiation.     

Comparison of three inbred lines of mice by overall and genetic radiosensitivity

The radiosensitivities of three mouse strains (BALB/cLacY, C3H/SnY, and 101/HY) have been compared using the following parameters: survival after irradiation at a dose of 6-7 Gy, chromosome aberration frequency in bone marrow cells after irradiation at a dose of 1.5 Gy, and the change in testis weight and frequency of abnormal sperm heads (ASHs) after irradiation at doses from 0.5 to 4 Gy. Strain BALB/c is the most radiosensitive with respect to the survival and chromosome aberration frequency in the bone marrow but the most resistant with respect to the change in testis weight and the frequency of abnormal sperm heads. Strain 101/HY was the most resistant with respect to survival and chromosome aberration frequency in bone marrow after irradiation but the most radiosensitive with respect to testis damage.     

In vivo mutant T cell frequency in atomic bomb survivors carrying outlying values of chromosome aberration frequencies

Frequencies of HPRT- mutant T cells were determined by means of a direct clonal assay in atomic bomb survivors who showed outlying values of chromosome aberration frequencies. The studied survivors consisted of 2 groups: those whose aberration frequency was near the higher end of the distribution (high-aberration group) and those whose aberration frequency was near the lower end of the distribution (low-aberration group). The mean radiation doses (T65D) of the high-aberration group (13 people) and low-aberration group (17 people) were 248 and 273 rad, respectively. The mean mutant frequency (Mf) of the high-aberration group was 6.7 X 10(-6), which was significantly higher than that of the low-aberration group (3.7 X 10(-6)) or that of 17 controls (3.4 X 10(-6)). When all the samples were combined, the correlation between Mf and radiation dose was not significant using either dose estimation system, T65D or DS86. However, the correlation coefficient was higher when DS86 doses were used. Mf correlated significantly with increasing aberration frequencies. The tendency that Mf correlates better with chromosome aberration frequency than with estimated radiation dose was stronger in this study than in a previous study where the samples were selected randomly.     

Improving Axial Resolution in Confocal Microscopy with New High Refractive Index Mounting Media

Resolution, high signal intensity and elevated signal to noise ratio (SNR) are key issues for biologists who aim at studying the localisation of biological structures at the cellular and subcellular levels using confocal microscopy. The resolution required to separate sub-cellular biological structures is often near to the resolving power of the microscope. When optimally used, confocal microscopes may reach resolutions of 180 nm laterally and 500 nm axially, however, axial resolution in depth is often impaired by spherical aberration that may occur due to refractive index mismatches. Spherical aberration results in broadening of the point-spread function (PSF), a decrease in peak signal intensity when imaging in depth and a focal shift that leads to the distortion of the image along the z-axis and thus in a scaling error. In this study, we use the novel mounting medium CFM3 (Citifluor Ltd., UK) with a refractive index of 1.518 to minimize the effects of spherical aberration. This mounting medium is compatible with most common fluorochromes and fluorescent proteins. We compare its performance with established mounting media, harbouring refractive indices below 1.500, by estimating lateral and axial resolution with sub-resolution fluorescent beads. We show furthermore that the use of the high refractive index media renders the tissue transparent and improves considerably the axial resolution and imaging depth in immuno-labelled or fluorescent protein labelled fixed mouse brain tissue. We thus propose to use those novel high refractive index mounting media, whenever optimal axial resolution is required.     

The Database for Analysis of Quantitative Characteristics of Chromosome Aberration Frequencies in the Culture of Human Peripheral Blood Lymphocytes

The data on spontaneous chromosome aberration rates in cultures of human peripheral blood lymphocytes obtained in the past 30 years have been collected to form a database. The database contains the results of analysis of more than 330 000 metaphases in lymphocytes from more than 1200 subjects. The frequency of aberrant metaphases in the control group has been estimated at 0.0213 ± 0.00085. No differences between sexes have been found with respect to either the total chromosome aberration rate or the rates of individual aberration types. The total chromosome aberration rate did not depend on age; however, it has been found that the number of fragments increased and the number of exchanges decreased with age. Smoking has been found to increase the frequency of chromosome aberrations in individuals with occupational hazards, but not in those who are not occupationally exposed to radiation or chemicals. Alcohol consumption increased the frequency of paired fragments, whereas the frequencies of other aberrations did not differ from the control values.     

The database for analysis of quantitative characteristics of chromosome aberration frequencies in the culture of human peripheral blood lymphocytes]

The data on spontaneous chromosome aberration rates in cultures of human peripheral blood lymphocytes obtained in the past 30 years have been collected to form a database. The database contains the results of analysis of more than 330,000 metaphases in lymphocytes from more than 1200 subjects. The frequency of aberrant metaphases in the control group has been estimated at 0.0213 +/- 0.00085. No differences between sexes have been found with respect to either the total chromosome aberration rate or the rates of individual aberration types. The total chromosome aberration rate did not depend on age; however, it has been found that the number of fragments increased and the number of exchanges decreased with age. Smoking has been found to increase the frequency of chromosome aberrations in individuals with occupational hazards, but not in those who are not occupationally exposed to radiation or chemicals. Alcohol consumption increased the frequency of paired fragments, whereas the frequencies of other aberrations did not differ from the control values.     

Proportional counter dosimetry and microdosimetry for radiotherapy with multiple pion beams

At the Swiss Institute for Nuclear Research (SIN) cancer patients are irradiated with negatively charged pi mesons using a 60-beam medical pion generator, the Piotron. A low-pressure tissue-equivalent proportional counter was used to measure absorbed dose and microdosimetric spectra. A method was developed to allow discrimination of events from different beam components, i.e., beam contamination (electrons and muons), pions in flight, and stopping pions. Measurements were performed along the axis and at lateral distances off one of these identical pion beams. The marked changes of total microdosimetric spectra with depth in phantom detected in earlier measurements are mainly due to large variations in the dose contributions of the beam components and much less to changes in the shapes of the individual microdosimetric spectra. The single beam measurements were used to calculate three-dimensional distributions of absorbed dose and of dose mean lineal energy, yD, for dynamic patient irradiations. Within the whole target volume yD remains nearly constant when irradiated with all 60 beams, whereas considerable changes were found for irradiations with 31 beams coming from a semicircle. Both size and shape of target volumes influence yD, the maximum values ranging from 30 to 45 keV/micron.     

Quantitative characteristics of the frequency of chromosomal aberrations in a group of residents of a large western Siberian industrial region

The results of a 15-year study of chromosome aberration frequency in cultured peripheral blood lymphocytes from subjects living in the Kuzbass industrial region are presented. The database for the analysis of the main parameters of chromosome aberrations contains data on 925 subjects, with the total number of cells examined being 92,900. It has been found that the total frequency of aberrant metaphases in the database is 3.73 +/- 0.1%, whereas this frequency for the sample of subjects from industrial areas of this region (the basic control group) is significantly lower (2.86 +/- 0.26%). It has been demonstrated that the sex and age of the subjects do not affect substantially the frequency of any type of chromosome aberrations. Tobacco smoking is associated with a slight increase in chromosome damage frequency; however, the difference between smokers and nonsmokers is insignificant even among subjects exposed to occupational hazards. The possible causes that have determined the increased basic and background chromosome aberration frequencies in the population of the Kemerovo oblast compared to these parameters for the European part of Russia and the CIS are discussed.     

Quantitative Characteristics of Chromosome Aberration Frequency in the Human Population of a Large Western Siberian Industrial Region

The results of a 15-year study of chromosome aberration frequency in cultured peripheral blood lymphocytes from subjects living in the Kuzbass industrial region are presented. The database for the analysis of the main parameters of chromosome aberrations contains data on 925 subjects, with the total number of cells examined being 92 900. It has been found that the total frequency of aberrant metaphases in the database is 3.73 ± 0.1%, whereas this frequency for the sample of subjects from industrial areas of this region (the basic control group) is significantly lower (2.86 ± 0.26%). It has been demonstrated that the sex and age of the subjects do not affect substantially the frequency of any type of chromosome aberrations. Tobacco smoking is associated with a slight increase in chromosome damage frequency; however, the difference between smokers and nonsmokers is insignificant even among subjects exposed to occupational hazards. The possible causes that have determined the increased basic and background chromosome aberration frequencies in the population of the Kemerovo oblast compared to these parameters for the European part of Russia and the CIS are discussed.     

Out-of-field doses from secondary radiation produced in proton therapy and the associated risk of radiation-induced cancer from a brain tumor treatment

PurposeTo determine out-of-field doses produced in proton pencil beam scanning (PBS) therapy using Monte Carlo simulations and to estimate the associated risk of radiation-induced second cancer from a brain tumor treatment.MethodsSimulations of out-of-field absorbed doses were performed with MCNP6 and benchmarked against measurements with tissue-equivalent proportional counters (TEPC) for three irradiation setups: two irradiations of a water phantom using proton energies of 78–147 MeV and 177–223 MeV, and one brain tumor irradiation of a whole-body phantom. Out-of-field absorbed and equivalent doses to organs in a whole-body phantom following a brain tumor treatment were subsequently simulated and used to estimate the risk of radiation-induced cancer. Additionally, the contribution of absorbed dose originating from radiation produced in the nozzle was calculated from simulations.ResultsOut-of-field absorbed doses to the TEPC ranged from 0.4 to 135 µGy/Gy. The average deviation between simulations and measurements of the water phantom irradiations was about 17%. The absorbed dose contribution from radiation produced in the nozzle ranged between 0 and 70% of the total dose; the contribution was however small in absolute terms. The absorbed and equivalent doses to the organs ranged between 0.2 and 60 µGy/Gy and 0.5–151 µSv/Gy. The estimated lifetime risk of radiation-induced second cancer was approximately 0.01%.ConclusionsThe agreement of out-of-field absorbed doses between measurements and simulations was good given the sources of uncertainties. Calculations of out-of-field organ doses following a brain tumor treatment indicated that proton PBS therapy of brain tumors is associated with a low risk of radiation-induced cancer.     

Cytogenetic investigation in lymphocytes of people living in cadmium-polluted areas

Chromosome aberrations were analyzed from peripheral lymphocyte cultures of 21 men and 19 women who had been exposed to environmental cadmium, and 11 controls (9 men and 2 women). The average cadmium level in the urine of the Cd-polluted group was 3.32 micrograms/l for men and 3.83 micrograms/l for women. There were significant differences in chromosome aberration frequencies between the Cd-polluted and non-polluted groups. The number of individuals with relatively high aberration frequencies (greater than or equal to 5%) in the Cd-polluted group was greater than in the controls. Individuals with a high cadmium content in urine (greater than or equal to 3 micrograms/l) had higher aberration frequencies and more severe aberration types in comparison with the low-cadmium group (less than 3 micrograms/l). There were significant correlations between chromosome aberration frequencies and urinary cadmium content (r = 0.463). The linear regression equation was determined. Considering the conflicting results in other published reports, it is hard to say that the conclusion that cadmium only acts synergistically to enhance the mutagenicity of other compounds present in the environment is correct. According to our study, environmental cadmium cannot only induce chromosome aberrations but also increases the chromosomal aberration frequencies and the frequency of severe aberration types.     

Measured microdosimetric spectra and therapeutic potential of boron neutron capture enhancement of 252Cf brachytherapy

Californium-252 is a neutron-emitting radioisotope used as a brachytherapy source for radioresistant tumors. Presented here are microdosimetric spectra measured as a function of simulated site diameter and distance from applicator tube 252Cf sources. These spectra were measured using miniature tissue-equivalent proportional counters (TEPCs). An investigation of the clinical potential of boron neutron capture (BNC) enhancement of 252Cf brachytherapy is also provided. The absorbed dose from the BNC reaction was measured using a boron-loaded miniature TEPC. Measured neutron, photon and BNC absorbed dose components are provided as a function of distance from the source. In general, the absorbed dose results show good agreement with results from other measurement techniques. A concomitant boost to 252Cf brachytherapy may be provided through the use of the BNC reaction. The potential magnitude of this BNC enhancement increases with increasing distance from the source and is capable of providing a therapeutic gain greater than 30% at a distance of 5 cm from the source, assuming currently achievable boron concentrations.     

Sister chromatid exchange in newborns

Summary Siter chromatid exchanges (SCE) were analyzed in the cord and postnatal blood of controlled groups of low and high birth weight infants to detect possible associations between abnormal birth weight and SCE frequency. Structural chromosome aberration rates had previously been evaluated for all infants, and possible correlations between aberration and SCE rates were sought.No correlation was found between neonatal or postnatal SCE frequency and birthweight, nor was there evidence of association of chromosome aberration rates with SCE frequency. In all groups of infants, however, mean postnatal SCE frequencies were significantly lower than mean neonatal SCE frequencies.