Chromosomal rearrangements induced in mouse spermatogonia by 14.5-MeV neutrons

Inbred CBA male mice were irradiated with 14.5-MeV neutrons. Three acute doses, 75, 150 and 250 rad, and one chronic dose, 250 rad, were given. The percentages of affected spermatocytes as counted from reciprocal translocations which had been induced in spermatogonia were 0.7, 0.8 and 1.6 respectively for the acute series and 2.2 after chronic exposure. The data could be fitted to a linear or concave curvilinear regression line. There seemed to be a slight increase of damage with dose, even if the percentages were generally lower than those reported earlier for fast neutrons with energies around 1 MeV. The existence of dose-rate effects is discussed, and the conclusion drawn so far is that there seems to be no such effect either for 1-MeV fast neutrons or 14.5-MeV high energy neutrons. The term “reversed dose-rate effect”, as used earlier, relates to another phenomenon. The difference between the point estimates for the chronic and acute 250 rad series is not significant. The effectiveness of neutrons with energies around 14 MeV versus neutrons with energies around 1 MeV is discussed.     

Oncogenic transformation by fractionated doses of neutrons

Oncogenic transformation was assayed after C3H 10T1/2 cells were irradiated with monoenergetic neutrons; cells were exposed to 0.23-, 0.35-, 0.45-, 5.9-, and 13.7-MeV neutrons given singly or in five equal fractions over 8 h. At the biologically effective neutron energy of 0.45 MeV, enhancement of transformation was evident with some small fractionated doses (below 1 Gy). When transformation was examined as a function of neutron energy at 0.5 Gy, enhancement was seen for cells exposed to three of the five energies (0.35, 0.45, and 5.9 MeV). Enhancement was greatest for cells irradiated with 5.9-MeV neutrons. Of the neutron energies examined, 5.9-MeV neutrons had the lowest dose-averaged lineal energy and linear energy transfer. This suggests that enhancement of transformation by fractionated low doses of neutrons may be radiation-quality dependent.     

Neutron RBEs and the radiosensitive target for mouse immature oocyte killing

The highly radiosensitive immature oocytes of mice were irradiated in vivo with graded doses of 252Cf fission radiation, 0.43- or 15-MeV neutrons, or 60Co gamma rays. Comparisons of oocyte survival for neutrons and for gamma rays demonstrate that neutron RBEs for the killing of these important cells do not reach the high values (30-50 or more) at low doses observed for several other biological end points. Rather, neutrons differ little in effectiveness from gamma rays in killing these extremely sensitive murine oocytes. For 0.43-MeV neutrons, RBEs obtained from fitted survival curves reach only 1.7 at 0.1 rad. For 15-MeV neutrons, they are not significantly different from 1 at any dose tested (lowest, 4.5 rad). For 252Cf fission neutrons (E = 2.15 MeV), RBEs are intermediate between those for 0.43- and 15-MeV neutrons. For all neutron energies tested, the RBEs are particularly low in the juvenile period, a time when murine immature oocytes are especially radiosensitive. With exposure just prior to birth, however, when these cells are much less easily killed, higher, more usual RBEs are found. The minimum size of the lethality target in mouse immature oocytes, estimated from the inactivation constant for 0.43-MeV neutrons and microdosimetric values, is larger than the nucleus but not larger than the cell. This and related analytical considerations suggest that the hypersensitive target in these particular oocytes is the plasma membrane, a finding which is in excellent accord with results from other experiments using different, contrasting radiations and dose deliveries (accelerated Si14+ ions, gamma rays, and beta rays from 3HOH compared with those from [3H]thymidine).     

Radiation quality and rat motor performance

The effects of bremsstrahlung, electron, gamma, and neutron radiations were investigated on the motor performance of male Sprague-Dawley rats. Rats were irradiated at a midline tissue dose rate of 20 Gy/min +/- 1 with one of the following: 18.6-MeV electrons (N = 40) or 18.1-MVp bremsstrahlung (N = 57) from a linear accelerator, 60Co 1.25-MeV gamma-ray photons (N = 48), or reactor neutrons at 1.67 MeV tissue-kerma weighted-mean energy (N = 43). Radiation effects were determined by establishing median effective doses (ED50) for rats trained on an accelerod, a shock-avoidance motor performance test. ED50's were based on 10-min postexposure performance. The ED50's were 61 Gy for electrons, 81 Gy for bremsstrahlung, 89 Gy for gamma-ray photons, and 98 Gy for neutrons. In terms of relative biological effectiveness to produce early performance decrement (10 min from the start of irradiation), significant differences existed between the electrons and the other three fields and between the bremsstrahlung and neutron fields. These differences could not be explained by macroscopic dose distribution patterns in the irradiated animals. The data imply that different radiation qualities are not equally effective at disrupting performance, with high-energy electrons being the most effective and neutrons the least.     

The cytogenetic effects of 22-MeV neutrons

22-MeV neutrons affecting the culture of human peripheral blood lymphocytes have been studied for their cytogenetic peculiarities. Linear character of the dependence of chromosome aberrations yield within the dose range of 0.2-4.0 Gy is noted. Relative biological efficiency of 22-MeV neutrons reaches the highest values at low doses (18.8-2.4). Pair fragments and dicentrics prevail in spectrum of aberrations.     

Radiobiological intercomparison of clinical neutron beams for growth inhibition in Vicia faba bean roots

Relative biological effectiveness (RBE) and oxygen enhancement ratio (OER) values of different neutron beams produced at the variable energy cyclotron "Cyclone" of Louvain-la-Neuve (Belgium) were determined. The neutrons were obtained by bombarding a beryllium target with 34-, 45-, 65-, or 75-MeV protons or with 50-MeV deuterons. The biological system was growth inhibition in Vicia faba bean roots. Taking the p(65) + Be neutron beam as a reference, RBE values were found equal to 1.36 +/- 0.2, 1.20 +/- 0.1, 1.00 (ref), 0.98 +/- 0.1, and 1.18 +/- 0.1, respectively; the doses corresponding to 50% growth inhibition were 0.39, 0.44, 0.53, 0.54, and 0.45 Gy. For the same beams, OER values were found equal to 1.55 +/- 0.1, 1.38 +/- 0.1, 1.29 +/- 0.1, 1.41 +/- 0.1, and 1.60 +/- 0.2, respectively.     

Life shortening in mice exposed to fission neutrons and gamma rays. VII. Effects of 60 once-weekly exposures

A total of 6316 B6CF1 mice were exposed to 60 equal once-weekly doses of 0.85-MeV fission neutrons (0.033 to 0.67 cGy per weekly fraction) or 60Co gamma rays (1.67 to 10 cGy per weekly fraction) and were observed until they died. The mean aftersurvival times showed that the dose-response curves for both neutron and gamma-ray exposures were indistinguishable from linear over all doses except the highest neutron dose. The relative biological effectiveness (RBE) for neutrons, calculated as the ratio of the initial slopes of the dose-response curves, was about 20 for both males and females. Essentially the same value was obtained by a number of other analyses of the data. Virtually all of the radiation-specific excess mortality could be attributed to tumors; after decrementation of the population for nontumor deaths, the value of the RBE was not significantly changed.     

Measurement of neutron-induced genetic damage in mouse immature oocytes

Recent experimental evidence concerning the nature of radiosensitive targets in mouse immature (resting) oocytes has led to new experimental designs that permit measurement of radiation-induced genetic damage in these important cells. We have previously reported initial results of the detection of genetic damage in mouse immature oocytes using monoenergetic 0.43-MeV neutrons. Here we provide a full report of our data and compare the genetic sensitivity of immature oocytes with those measured by others for maturing oocytes. Until recently, all attempts to detect radiation-induced genetic damage in mouse immature oocytes had failed. This appears to have been because the radiation types and modes of dose delivery used in those studies did not sufficiently spare the hypersensitive lethality target (the plasma membrane) while at the same time deposit enough dose in DNA to produce detectable mutation. Recoil protons from 0.43-MeV neutrons produce short ionization tracks (2.6 micron mean) and can therefore deposit energy in the DNA without simultaneously traversing the plasma membrane. Using these particles, we have obtained dose-response relationships for both chromosome aberrations and dominant lethal mutations in oocytes from females irradiated 8-12 weeks earlier, when oocytes were immature. Results suggest that the intrinsic mutational sensitivity of mouse immature oocytes is not very different from that of maturing oocytes.     

Simulation and optimization of cyclic activation Analysis of short-lived isotopes with 14MeV neutron generator

Biological Trace Element Research - A program of simulation and optimization is developed for the case of cyclic activation analysis of short-lived isotopes with 14-MeV neutrons. The background...     

Effect of pulsed dose in simultaneous and sequential irradiation of V-79 cells by 14.8-MeV neutrons and 60Co photons

The effect of irradiating V-79 Chinese hamster cells with a mixture of 40% 14.8-MeV neutrons and 60% 60Co photons with simultaneous or sequential exposures is investigated. Sample doses are obtained by irradiating cells with alternating 3-min pulses of neutrons and photons (in the sequential case) or with mixed neutrons and photons followed by equal beam-off periods to ensure equal total exposure times for sequential and simultaneous irradiations. Differences between the survival results under each beam configuration that are consistent with previous observations with nonpulsed irradiations are observed.     

Analysis of biological samples using prompt gamma radions induced by 14.7-MeV neutrons

We investigate a method for determining the elemental composition of biological samples that uses prompt gamma rays induced by 14.7-MeV neutrons. Alpha particles are produced simultaneously with the neutrons, which exit opposite the alpha detector through the vacuum chamber wall. The sample under investigation is irradiated and emits gamma radiations in a spectral energy distribution characteristic of the material. Barium-fluoride (BaF₂) and high-purity germanium (HPGe) gamma detectors view the sample and record the spectrum of gamma radiation.

     

Hyperthermia increases chromosome breakage and loss induced by fission neutrons in Drosophila melanogaster

Pretreatment with hyperthermia did significantly increase the breakage and chromosome loss induced by 0.85-MeV fission neutrons from the JANUS biological research reactor in spermatozoa, early and late spermatids and spermatocytes. Radiation-induced breakage of chromosomes was also enhanced by hyperthermia in early spermatogonia.     

Neutrons and X-rays, comparative studies with Drosophila melanogaster. 2. Sex-chromosome loss and partial loss, evidence for the induction of chromatid aberrations in spermatozoa

Losses and duplications of BSY y+-chromosome markers were induced by irradiation of spermatozoa with either 0.5-MeV neutrons or 100-kV X-rays. These 2 types of radiation are known to induce significantly different ratios of double:single strand breaks in DNA. Exceptional progeny were grouped into 3 categories; no Y marker, one Y marker, and Y marker duplications + mosaics. The last combination consisted of exceptions derived from only chromatid-type rearrangements. All other classes of exceptions may be derived from either chromatid- or chromosome-type rearrangements. Doses of 15 Gy neutrons and 27 Gy X-rays induced identical frequencies of exceptional progeny, giving an RBE of 1.8. The ratios of the 3 classes of exceptions were similar for both types of radiation. This observation can be interpreted as indicating that, under the conditions used here, chromosome and chromatid rearrangements are not derived directly from double and single DNA strand breaks, respectively.     

Neutron-energy-dependent oncogenic transformation of C3H 10T1/2 mouse cells

The relative biological effectiveness (RBE) of a range of neutron energies relative to 250-kVp X rays has been determined for oncogenic transformation and cell survival in the mouse C3H 10T 1/2 cell line. Monoenergetic neutrons at 0.23, 0.35, 0.45, 0.70, 0.96, 1.96, 5.90, and 13.7 MeV were generated at the Radiological Research Accelerator Facility of the Radiological Research Laboratories, Columbia University, and were used to irradiate asynchronous cells at low absorbed doses from 0.05 to 1.47 Gy. X irradiations covered the range 0.5 to 8 Gy. Over the more than 2-year period of this study, the 31 experiments provided comprehensive information, indicating minimal variability in control material, assuring the validity of comparisons over time. For both survival and transformation, a curvilinear dose response for X rays was contrasted with linear or nearly linear dose responses for the various neutron energies. RBE increased as dose decreased for both end points. Maximal RBE values for transformation ranged from 13 for cells exposed to 5.9-MeV neutrons to 35 for 0.35-MeV neutrons. This study clearly shows that over the range of neutron energies typically seen by nuclear power plant workers and individuals exposed to the atomic bombs in Japan, a wide range of RBE values needs to be considered when evaluating the neutron component of the effective dose. These results are in concordance with the recent proposals in ICRU 40 both to change upward and to vary the quality factor for neutron irradiations.     

Dose-response relationships and R.B.E. values of dominant lethals induced by X-rays and 1.5 MeV neutrons in prophase-1 oocytes and in mature sperm of the two-spotted spider mite Tetranychus urticae Koch (acari, tetranychidae)

Mature sperm and prophase-1 oocytes of Tetranychus urticae Koch were irradiated with 250-kVp X-rays or 1.5 MeV fast neutrons. The X-ray doses ranged from 0.5 to 24.0 krad, and those of the fast neutrons from 0.1 to 16.0 krad. The genetic endpoint measured was lethality, expressed in the stages from egg to adulthood in the F1 progeny. The frequency of recessive lethals in female germ cells was estimated by comparing survival of fertilized versus unfertilized F1 eggs, after irradiation with the same dosage. X-Rays induce dominant lethals in prophase-1 oocytes by the action of both single hits on single targets and multiple hits on multiple targets. 1.5-MeV neutrons induce these effects predominantly by the action of multiple tracks on multiple targets. Dominant lethals were induced in mature sperm by X-rays and by fast neutrons by the action of both single hits on single targets and multiple hits on multiple targets. Both for prophase-1 oocytes and for mature sperm the low R.B.E. value corresponded with the relatively large multiple-target component of induction of dominant lethals by fast neutrons. The nature of dominant lethality in relation to the kinetochore organization of the chromosome is discussed. A non-linear trend in the dose--effect relationship was observed for both X-rays and fast neutrons for the estimated frequency of recessive lethals induced in prophase-1 oocytes. X-Rays were more effective than neutrons in inducing recessive lethals in prophase-1 oocytes at doses lower than 3 krad.     

Cytogenetic effects induced by neutrons in human peripheral blood lymphocytes in vitro. I. Dose-effect relationship for different types of chromosome aberrations when exposed to neutrons with different energies]

Human lymphocytes were irradiated in vitro during G0 stage by graded doses of thermal neutrons and of neutrons with mean energy of 0.04; 0.09; 0.35; 0.85 and 14.7 MeV as well as by 60Co gamma-rays. The data were fitted to the linear and linear-quadratic relations. The neutrons of low and intermediate energies showed the linear dependence on the dose, 14.7 MeV neutrons and gamma-rays--a linear-quadratic one, whereas the data obtained with 0.85 MeV neutrons fitted well the both models. Terminal and interstitial deletions produced by both gamma-rays and neutrons showed different dependencies upon the dose. Some qualitative pecularities of aberration spectra were found in the experiments with neutrons as compared with the data on gamma-irradiation: the ratio of exchanges to fragments was greater, and aberrations of chromatid type were produced. The specially designed experiments and calculations showed that the last effect was not connected with induced radioactivity.     

RBEs of thermal neutron capture therapy and 10B(n, alpha)7 Li reaction on melanoma-bearing hamsters

Using Greene's melanoma transplanted into Syrian (golden) hamsters, we determined the relative biological effectiveness (RBE) of thermal neutron capture therapy (TNCT) using 10B-paraboronophenylalanine (10B-BPA) in comparison with a 9-MeV electron beam. We also obtained the RBE of the 10B(n, alpha)7 Li reaction by calculation based on summed dose data from TNCT. Throughout this study, the Kyoto University Research Reactor was used as the source for thermal neutrons; the reactor was specially altered to attain a low contamination level both for gamma-rays and fast neutrons. 10B-BPA was administered 8 hours before thermal neutron irradiation to the hamsters with melanoma. The tumor was then irradiated at 5 MW for 90 minutes. The absorbed dose from this TNCT was calculated by the method of Fairchild and Goodman (Phys. Med. Biol. 1966; 2:15-30). The RBEs of the TNCT and the 10B(n, alpha)7 Li reaction obtained by the tumor growth delay time (TGDT) method were 2.22 and 2.51, respectively, at 10.5 days of TGDT. These RBE values varied with TGDT and the absorbed dose. The RBE value of TNCT had a peak at 7.0 days of TGDT; that of the 10B(n, alpha)7Li reaction was higher at a low absorbed dose level and lower at a high absorbed dose level.     

The relative biological effectiveness of 14.5-MeV neutrons for the induction of gene conversion and mutation in yeast

The relative biological effectiveness (RBE) and oxygen enhancement ratio (OER) were determined in the yeast Saccharomyces cerevisiae for the induction of gene conversion (the product of recombinational repair) and mutation (the product of error prone repair) by 14.5-MeV neutrons in comparison with 60Co gamma rays and 150 KVp X rays. Neutron irradiation in oxic or anoxic conditions induced significantly higher yields of convertants and mutants than sparsely ionizing radiations under the same conditions. RBEs for both gene conversion and mutation under anoxia were significantly higher than under oxic conditions. RBEs for mutant induction under anoxia were lower than the RBEs for gene conversion under the same conditions. The data support the hypothesis that the production of lesions leading to the genetic consequences of gene conversion and mutation differ in their dependence upon LET and the presence of oxygen during irradiation, and therefore the two DNA repair processes which produce these end points recognize, at least in part, different classes of damage.     

Relative biological effectiveness measurements using murine lethality and survival of intestinal and hematopoietic stem cells after fermilab neutrons compared to JANUS reactor neutrons and 60Co gamma rays

The relative biological effectiveness (RBE) of the 25-MeV (average energy) neutron beam at the Fermi National Accelerator Laboratory was measured using murine bone marrow (LD50/30) and gut (LD50/6) lethality and killing of hematopoietic colony forming units (CFU-S) or intestinal clonogenic cells (ICC). The reference radiation was 60Co gamma rays. The LD50/30 and LD50/6 for mice exposed to the Fermilab neutron beam were 6.6 and 8.7 Gy, respectively, intermediate between those of JANUS neutrons and 60Co gamma rays. The D0 values for CFU-S and ICC were 47 cGy and 1.05 Gy, respectively, also intermediate between the lowest values found for JANUS neutrons and the highest values found after 60Co gamma rays. The split-dose survival ratios for CFU-S at intervals of 1-6 hr between doses were essentially 1.0 for both neutron sources, while the corresponding split-dose survival ratio for 60Co gamma rays was consistantly above 1, reaching a maximum of 1.7 with a 1-hr interval between doses. The 3-hr split-dose survival ratios for ICC were 1.0 for JANUS neutrons, 1.85 for Fermilab neutrons, and 6.5 for 60Co gamma rays. The RBE estimates for LD50/30 were 1.5 and 2.3 for Fermilab and JANUS neutrons, respectively. Based on LD50/6, the RBEs were 1.9 (Fermilab) and 3.0 (JANUS). The RBEs for CFU-S D0 were 1.4 (Fermilab) and 1.9 (JANUS) and for jejunal microcolony D0 1.4 (Fermilab) and 2.8 (JANUS).     

Monte Carlo characterizations mapping of the (γ,n) and (n,γ) photonuclear reactions in the high energy X-ray radiation therapy

Aim

The aim of this work was to map the characteristics of (n,γ) and (γ,n) reactions in a high energy photon radiation therapy.

Background

Photoneutrons produced in the high energy X-Ray radiation therapy may damage patients and staff. It is due to high RBE of the produced neutrons according to their energy and isotropic emission. Characterization of the photoneutrons can help us in appropriate shielding.

Materials and methods

This study focused on the photoneutron and capture gamma ray phenomena. Characteristics such as dose value, fluence and spectra of both the neutrons and the by produced prompt gamma ray were described.

Results and discussion

Neutron and prompt gamma spectra in different points showed the neutrons to be thermalized when increasing the distance from the linac. Energy of the neutrons changed from about 0.6 MeV at the isocentre to around 10⁻⁰⁸ MeV at the outer door position. Although the neutrons were found as fast neutrons, their spectra showed they were thermal neutrons at the outer door position. Additionally, it was seen that the energy of the gamma rays is higher than the scattered X-ray energy. The energy of gamma rays was seen to be up to 10 MeV while the linac photons had energy lower than 1 MeV. Neutron source strength obtained in this work was in good agreement with the published data, which may be a confirmation of our simulation accuracy.

Conclusion

The study showed that the Monte Carlo simulation can be applied in the radiotherapy and industrial radiation works as a useful and precise estimator. We also concluded that the dose from the prompt gamma ray at the outer door location is higher than the scattered radiation from the linac and should be considered in the shielding.