Relative biological effectiveness of 144 keV neutrons in producing dicentric chromosomes in human lymphocytes compared with 60Co gamma rays under head-to-head conditions

The RBE for neutrons was assessed in a head-to-head experiment in which cultures of lymphocytes from the same male donor were irradiated simultaneously with 144 keV neutrons and with 60Co gamma rays as the reference radiation and evaluated using matched time, culture conditions, and the end point of chromosomal aberrations to avoid potential confounding factors that would influence the outcome of the experiment. In addition, the irradiation time was held constant at 2 h for the high-dose groups for both radiation types, which resulted in rather low dose rates. For the induction of dicentric chromosomes, the exposure to the 144 keV neutrons was found to be almost equally as effective (yield coefficient alpha(dic) = 0.786 +/- 0.066 dicentrics per cell per gray) as that found previously for irradiation with monoenergetic neutrons at 565 keV (alpha(dic) = 0.813 +/- 0.052 dicentrics per cell per gray) under comparable exposure and culture conditions (Radiat. Res. 154, 307-312, 2000). However, the values of the maximum low-dose RBE (RBE(m)) relative to 60Co gamma rays that were determined in the present and previous studies show an insignificant but conspicuous difference: 57.0 +/- 18.8 and 76.0 +/- 29.5, respectively. This difference is mainly due to the difference in the alpha(dic) value of the 60Co gamma rays, the reference radiation, which was 0.0138 +/- 0.0044 Gy(-1) in the present study and 0.0107 +/- 0.0041 Gy(-1) in the previous study. In the present experiment, irradiations with 144 keV neutrons and 60Co gamma rays were both performed at 21 degrees C, while in the earlier experiment irradiations with 565 keV neutrons were performed at 21 degrees C and the corresponding reference irradiation with gamma rays was performed at 37 degrees C. However, the temperature difference between 21 degrees C and 37 degrees C has a minor influence on the yield of chromosomal alterations and hence RBE values. The large cubic PMMA phantom that was used for the gamma irradiations in the present study results in a larger dose contribution from Compton-scattered photons compared to the mini-phantom used in the earlier experiments. The contribution of these scattered photons may explain the large value of alpha(dic) for gamma irradiation in the present study. These results indicate that the yield coefficient alpha(dic) for 144 keV neutrons is similar to the one for 565 keV neutrons, and that modification of the alpha(dic) value of the low-LET reference radiation, due to changes in the experimental conditions, can influence the RBE(m). Consequently, alpha(dic) values cannot be shared between cytogenetic laboratories for the purpose of assessment of RBM(m) without verification of the comparability of the experimental conditions.     

Recovery of murine lens epithelial cells from single and fractionated doses of X rays and neutrons

Subpopulations of mouse lens epithelial cells, differing in proliferative status, were irradiated with either X rays or fission spectrum neutrons given singly or in four weekly fractions. After various times, epithelia were mitogenically stimulated by wounding and DNA synthesis responses were determined by incorporation of [3H]thymidine. At 1 h following both X and neutron irradiations, significant suppression of the wound response after single doses and a sparing effect of fractionation were evident in both the mitotically quiescent and the slowly proliferating subpopulations. At 1 week following single or fractionated doses of both radiations, recovery was evident in both subpopulations. By 4 weeks, the quiescent subpopulation showed significant recovery after both single and fractionated doses of X rays or neutrons. In contrast, a marked decreased ability to respond after neutron irradiation and, in addition, a significant enhancement effect of neutron fractionation were observed for the slowly proliferating subpopulation. Per gray, neutrons were about 7.5 times more effective than X rays as a single dose and 25 times more effective in four equal fractions. The shift from an initial sparing to a final enhancing effect of neutron fractionation for the slowly proliferating subpopulation has importance for understanding divergent early and late radiation responses following dose fractionation.     

The influence of hypoxia on the relative sensitivity of human tumor cells to 62.5 MeV (p-->Be) fast neutrons and 4 MeV photons

Fast neutrons have been used in the clinical radiation therapy of tumors largely because of experimental evidence that their cytotoxic effects are much less dependent on oxygen levels than those of low-LET photons. The potential therapeutic advantage of fast neutrons based on hypoxia alone can be calculated as the "hypoxic gain factor", which is the ratio of the OERs for the fast-neutron compared to the photon beams. The hypoxic gain factor that is generally anticipated based on studies with established mammalian cell lines is about 1.6. However, surprisingly few studies have examined the influence of hypoxia on the fast-neutron radiosensitivity of human tumor cells of different histological types. For this reason, we have determined the OERs of five human tumor cell lines exposed to 62.5 MeV (p-->Be) cyclotron-generated fast neutrons or 4 MeV photons from a clinical linear accelerator. The OERs for four chemotherapy-naive cell lines, HT29/5, Hep2, HeLa and RT112, were invariably greater for photons than for neutrons, but all of these values were lower than expected on the basis of the previous literature. Despite their low OERs, these cell lines showed hypoxic gain factors that were within the range of 1.31-1.63, indicating that such effects cannot entirely explain the disappointing clinical results obtained with fast neutrons. In contrast, comparison of the surviving fractions at clinically relevant doses (1.6 Gy of neutrons and 2.0 Gy of photons) for these four tumor cell lines suggested that little benefit should result from neutron treatment. Only the cisplatin-resistant OAW42-CP line showed a significant hypoxic gain factor by this method of analysis. We conclude that, at the dose fractions used in clinical radiation therapy, there may not be a radiobiological precedent for higher local control rates after fast-neutron irradiation of hypoxic tumor cells.     

Evaluation of energy deposition and secondary particle production in proton therapy of brain using a slab head phantom

AimEvaluation of energy deposition of protons in human brain and calculation of the secondary neutrons and photons produced by protons in proton therapy.BackgroundRadiation therapy is one of the main methods of treating localized cancer tumors. The use of high energy proton beam in radiotherapy was proposed almost 60 years ago. In recent years, there has been a revival of interest in this subject in the context of radiation therapy. High energy protons suffer little angular deflection and have a well-defined penetration range, with a sharp increase in the energy loss at the end of their trajectories, namely the Bragg peak.Materials and methodsA slab head phantom was used for the purpose of simulating proton therapy in brain tissue. In this study simulation was carried out using the Monte Carlo MCNPX code.ResultsBy using mono energetic proton pencil beams, energy depositions in tissues, especially inside the brain, as well as estimating the neutron and photon production as a result of proton interactions in the body, together with their energy spectra, were calculated or obtained. The amount of energy escaped from the head by secondary neutrons and photons was determined.ConclusionsIt was found that for high energy proton beams the amount of escaped energy by neutrons is almost 10 times larger than that by photons. We estimated that at 110 MeV beam energy, the overall proton energy “leaked” from the head by secondary photons and neutrons to be around 1%.     

Ex vivo determination of the effect of whole-body exposure to fast neutrons on murine spleen cell viability and apoptosis

The effects of high-linear energy transfer (LET) radiations on lymphoid tissues and lymphocytes are not well understood. As a first approach to delineate these effects, the present work was conducted to assess the effects of high-LET radiations on murine spleen cells ex vivo and in vitro. BALB/c mice were irradiated whole-body with 65 MeV neutrons or 15 MV X rays at doses ranging from 0.2 to 3 Gy. Spleens were removed 1 day postirradiation and weighed, and single cell suspensions were prepared and cultured for several days. Apoptosis occurring in vitro was determined at different times by flow cytometry analysis of cells labeled with propidium iodide. It was found that irradiation with fast neutrons reduced spleen weight and cellularity to a greater extent than photons. Considering the spleen cellularity as end point, the relative biological effectiveness (RBE) of fast neutrons was 2. However, for both modes of irradiation, apoptosis of recovered spleen cells in vitro increased as a function of dose and the duration of culture. The level of apoptosis occurring at various times postirradiation was found to be identical for high- and low-LET radiations. Taken together, these results suggest that external as well as cellular factors might differentially modulate the sensitivity of lymphocytes to fast neutrons and photons.     

A comparison of gamma and neutron irradiation on Raji cells: effects on DNA damage, repair, cell cycle distribution and lethality.

The Comet assay (microgel electrophoresis) was used to study DNA damage in Raji cells, a B-lymphoblastoid cell line, after treatment with different doses of neutrons (0.5 to 16 Gy) or gamma rays (1.4 to 44.8 Gy). A better growth recovery was observed in cells after gamma-ray treatments compared with neutron treatments. The relative biological effectiveness (RBE) of neutron in cell killing was determined to be 2.5. Initially, the number of damaged cells per unit dose was approximately the same after neutron and gamma-ray irradiation. One hour after treatment, however, the number of normal cells per unit dose was much lower for neutrons than for gamma rays, suggesting a more efficient initial repair for gamma rays. Twenty-four hours after treatment, the numbers of damaged cells per unit dose of neutrons or gamma rays were again at comparable level. Cell cycle kinetic studies showed a strong G2/M arrest at equivalent unit dose (neutrons up to 8 Gy; gamma rays up to 5.6 Gy), suggesting a period in cell cycle for DNA repair. However, only cells treated with low doses (up to 2 Gy) seemed to be capable of returning into normal cell cycle within 4 days. For the highest dose of neutrons, decline in the number of normal cells seen at already 3 days after treatment was deeper compared with equivalent unit doses of gamma rays. Our present results support different mechanisms of action by these two irradiations and suggest the generation of locally multiply damaged sites (LMDS) for high linear energy transfer (LET) radiation which are known to be repaired at lower efficiency.     

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.     

An assessment of the behavioral toxicity of high-energy iron particles compared to other qualities of radiation

Conditioned taste aversion was used to evaluate the behavioral toxicity of exposure to high-energy iron particles (56Fe, 600 MeV/amu) in comparison to that of gamma photons (60Co), high-energy electrons, or fission neutrons. Exposure to high-energy iron particles (5-500 cGy) produced a dose-dependent taste aversion with a maximal effect achieved with a dose of 30 cGy. Gamma photons and electrons were the least effective stimuli for producing a conditioned taste aversion, with a maximal aversion obtained only after exposure to 500 cGy, while the effectiveness of fission neutrons was intermediate to that of photons and iron particles, and a maximal aversion was obtained with a dose of 100 cGy. In the second experiment, rats with lesions of the area postrema were exposed to iron particles (30 cGy), but failed to acquire a taste aversion. The results indicate that (1) high-energy iron particles are more toxic than other qualities of radiation and (2) similar mechanisms mediate the behavioral toxicity of gamma photons and high-energy iron particles.     

Evaluation of the relative biological effectiveness of a clinical epithermal neutron beam using dog brain

This investigation was designed to determine the relative biological effectiveness (RBE) of an epithermal neutron beam (FiR 1 beam) using the brains of dogs. The FiR 1 beam was developed for the treatment of patients with glioma using boron neutron capture therapy. Comparisons were made between the effects of whole-brain irradiation with epithermal neutrons and 6 MV photons. For irradiations with epithermal neutrons, three dose groups were used, 9.4 +/- 0.1, 10.2 +/- 0.1 and 11.5 +/- 0.2 Gy. These physical doses were given as a single exposure and are quoted at the 90% isodose. Four groups of five dogs were irradiated with single doses of 10, 12, 14 or 16 Gy of 6 MV photons to the 100% isodose. Different reference isodoses were used to obtain the most comparable dose distribution in the brain for the two different irradiation modalities. Sequential magnetic resonance images (MRI) were taken for 77-115 weeks after irradiation to detect changes in the brain. Dose-effect relationships were established for changes in the brain as detected either by MRI or by subsequent gross morphology and histology. The doses that caused a specified response in 50% of the animals (ED(50)) were calculated from these dose-effect curves for each end point, and these values were used to calculate the RBE values for the different end points. The RBE values for the FiR 1 beam, based on changes observed on MRI, were in the range 1.2-1.3. For microscopic and gross pathological lesions, the values were in the range 1.2-1.4. The corresponding RBE values for the MRI and pathological end points for the high-LET components (protons from nitrogen capture and recoil protons from fast neutrons) were in the ranges 3.5-4.0 and 3.4-4.4, respectively. This assumed a dose-rate reduction factor of 0.6 for the low-dose-rate gamma-ray component of this beam. Finally, a comparison was made between experimentally derived photon doses, for a specified end point, with calculated photon equivalent doses, which were obtained using the weighting factors for clinical studies on the epithermal neutron beam on the Brookhaven Medical Research Reactor (BNL) in New York. This indicated that the radiation-induced lesions seen in the present study were, on average, detected at a 12% lower photon dose than predicted by the use of the BNL clinical weighting factors. This indicates the need for caution in the extrapolation of results from one reactor-based epithermal neutron beam to another.     

Neoplastic transformation is enhanced by multiple low doses of fission-spectrum neutrons

The neoplastic transformation of C3H mouse 10T1/2 cells was measured induced by fission-spectrum neutrons delivered at a high dose rate in five fractions over 4 days. The transformation frequency was significantly enhanced over that due to single equivalent total doses. These new data, in the low dose region, demonstrate an increased transformation frequency by fractionated versus single exposures of high-dose-rate fission-spectrum neutrons; an increase equal to that observed with low-dose-rate fission-spectrum neutrons (i.e., 0.086 rad/min). Estimates of the dose modifying factor (DMF), based upon the ratio of the initial linear portions of the induction curves for high and for low dose rates, suggest the same DMF (approximately 7.8) for both five daily fractions of high-dose-rate neutrons and for low-dose-rate neutrons. However, when these results are compared to those following high-dose-rate 60Co gamma rays (100 rad/min), the relative biological effectiveness (RBE) for low-dose-rate fission-spectrum neutrons based upon slope ratios is 19.6; similarly, the RBE relative to five daily fractions of 60Co gamma rays is 78.8.     

Effects of single and split doses of cobalt-60 gamma rays and 14 MeV neutrons on mouse stem cell spermatogonia

The long-term effects of ionizing radiation on male gonads may be the result of damage to spermatogonial stem cells. Doses of 10 cGy to 15 Gy (60)Co gamma rays or 10 cGy to 7 Gy 14 MeV neutrons were given to NMRI mice as single or split doses separated by a 24-h interval. The ratios of haploid spermatids/2c cells and the coefficients of variation of DNA histogram peaks as measures of both the cytocidal and the clastogenic actions of radiation were analyzed by DNA flow cytometry after DAPI staining. The coefficient of variation is not only a statistical examination of the data but is also used here as a measure of residual damage to DNA (i.e. a biological dosimeter). Testicular histology was examined in parallel. At 70 days after irradiation, the relative biological effectiveness for neutrons at 50% survival of spermatogonial stem cells was 3.6 for single doses and 2.8 for split doses. The average coefficient of variation of unirradiated controls of elongated spermatids was doubled when stem cells were irradiated with single doses of approximately 14 Gy (60)Co gamma rays or 3 Gy neutrons and observed 70 days later. Split doses of (60)Co gamma rays were more effective than single doses, doubling DNA dispersion at 7 Gy. No fractionation effect was found with neutrons with coefficients of variation.     

Lung carcinomas in Sprague-Dawley rats after exposure to low doses of radon daughters, fission neutrons, or gamma rays

The effectiveness of radon-daughter inhalation and irradiation with fission neutrons and gamma rays in the induction of lung carcinomas in Sprague-Dawley rats at low doses is compared. Earlier reports which compared radon-daughter inhalations and neutron irradiations over a wider range of doses were based on dosimetry for the radon-daughter inhalations which has recently been found to be faulty. In the present analysis, low-dose experiments were designed to derive revised equivalence ratios between radon-daughter exposures, and fission neutron or gamma irradiations. The equivalence is approximately 15 working level months (WLM) of radon daughters to 10 mGy of neutrons (the earlier value was 30 WLM to 10 mGy). The relative biological effectiveness (RBE) of neutrons is 50 or more at a gamma-ray dose of 1 Gy. In these experiments with low doses and exposures, the lifetime incidences can be estimated from the raw incidences, while the derivation of the time dependence of the prevalence is essential for the estimation of RBE values and equivalence ratios.     

Effective dose of A-bomb radiation in Hiroshima and Nagasaki as assessed by chromosomal effectiveness of spectrum energy photons and neutrons

The effective dose of combined spectrum energy neutrons and high energy spectrum γ-rays in A-bomb survivors in Hiroshima and Nagasaki has long been a matter of discussion. The reason is largely due to the paucity of biological data for high energy photons, particularly for those with an energy of tens of MeV. To circumvent this problem, a mathematical formalism was developed for the photon energy dependency of chromosomal effectiveness by reviewing a large number of data sets published in the literature on dicentric chromosome formation in human lymphocytes. The chromosomal effectiveness was expressed by a simple multiparametric function of photon energy, which made it possible to estimate the effective dose of spectrum energy photons and differential evaluation in the field of mixed neutron and γ-ray exposure with an internal reference radiation. The effective dose of reactor-produced spectrum energy neutrons was insensitive to the fine structure of the energy distribution and was accessible by a generalized formula applicable to the A-bomb neutrons. Energy spectra of all sources of A-bomb γ-rays at different tissue depths were simulated by a Monte Carlo calculation applied on an ICRU sphere. Using kerma-weighted chromosomal effectiveness of A-bomb spectrum energy photons, the effective dose of A-bomb neutrons was determined, where the relative biological effectiveness (RBE) of neutrons was expressed by a dose-dependent variable RBE, RBE(γ, D _n), against A-bomb γ-rays as an internal reference radiation. When the newly estimated variable RBE(γ, D _n) was applied to the chromosome data of A-bomb survivors in Hiroshima and Nagasaki, the city difference was completely eliminated. The revised effective dose was about 35% larger in Hiroshima, 19% larger in Nagasaki and 26% larger for the combined cohort compared with that based on a constant RBE of 10. Since the differences are significantly large, the proposed effective dose might have an impact on the magnitude of the risk estimates deduced from the A-bomb survivor cohort.     

Induction of pigmentation by continuous X-irradiation of amelanotic tumors of B16-XI mouse melanoma and induced change in chromosomes of amelanotic cells

Non-pigmented tumor cells of B16-XI mouse melanoma were found to contain a diploid number of chromosomes similarly to those of melanotic tumors and the parental cells in tissue culture. A major difference between pigmented and non-pigmented cells was in the number of biarmed chromosomes per cell. There was no difference in growth rate between non-pigmented and pigmented tumors, but growth usually begins about 2 days earlier in the former. Pigmentation lost in the course of serial transplantation was restored by irradiating the non-pigmented tumor continuously with 2,500-3,000 rads/passage of X-rays during six transfer generations. In the course of repeated irradiations, the chromosomes changed structurally and numerically as the pigmentation of the tumor was gradually restored. The observations of tumor growth and chromosomal changes are discussed in relation to the pigmentation of B16-XI melanoma cells.     

The interaction between X-rays and 3 MeV neutrons in the skin of the mouse foot

Mouse feet were irradiated with mixtures of 3 MeV neutrons and 140 kVp X-rays given simultaneously or within 24 hours of each other. The effects of different treatments were contrasted by comparing the doses required to give equal skin reactions. Irradiation was given as 1, 2, 4 or 8 equal fractions, in order to assess r.b.e. and the shapes of the underlying dose-response curves for mixed beams over a wide range of dose per fraction. All dose-effect curves were well fitted by a linear-quadratic (alpha, beta) model. For X-rays and neutrons given simultaneously, the linear coefficient (alpha) decreased by a factor of 4.80 while the quadratic coefficient (beta) increased by a factor of only 1.44 when the proton contamination in the beam increased from 11 to 100 per cent, with alpha/beta changing from 95.0 to 13.8. The data from simultaneous X-ray and neutron irradiation were consistent with full interaction of those effects from the two radiations which give rise to the total quadratic component of effect. When the two radiations are separated by up to 24 h, this interaction decreases but does not entirely disappear.     

Dose-response modeling of life shortening in a retrospective analysis of the combined data from the JANUS program at Argonne National Laboratory

Life shortening was investigated in both sexes of the B6CF1 (C57BL/6 x BALB/c) mouse exposed to fission neutrons and 60Co gamma rays. Three basic exposure patterns for both neutrons and gamma rays were compared: single exposures, 24 equal once-weekly exposures, and 60 equal once-weekly exposures. Ten different dose-response models were fitted to the data for animals exposed to neutrons. The response variable used for all dose-response modeling was mean after-survival. A simple linear model adequately described the response to neutrons for females and males at doses less than or equal to 80 cGy. At higher neutron dose levels a linear-quadratic equation was required to describe the life-shortening response. An effect of exposure pattern was observed prior to the detection of curvature in the dose response for neutrons and emerged as a potentially significant factor at neutron doses in the range of 40-60 cGy. Augmentation of neutron injury with dose protraction was observed in both sexes and began at doses as low as 60 cGy. The life-shortening response for all animals exposed to gamma rays (22-1918 cGy) was linear and inversely dependent upon the protraction period (1 day, 24 weeks, 60 weeks). Depending on the exposure pattern used for the gamma-ray baseline, relative biological effectiveness (RBE) values ranged from 6 to 43. Augmentation, because it occurred only at higher levels of neutron exposure, had no influence on the estimation of RBEm.     

Analysis of the EBT3 Gafchromic film irradiated with 6 MV photons and 6 MeV electrons using reflective mode scanners

We explore in our study the effects of electrons and X-rays irradiations on the newest version of the Gafchromic EBT3 film. Experiments are performed using the Varian “TrueBeam 1.6” medical accelerator delivering 6 MV X-ray photons and 6 MeV electron beams as desired. The main interest is to compare the responses of EBT3 films exposed to two separate beams of electrons and photons, for radiation doses ranging up to 500 cGy. The analysis is done on a flatbed EPSON 10000 XL scanner and cross checked on a HP Scanjet 4850 scanner. Both scanners are used in reflection mode taking into account landscape and portrait scanning positions. After thorough verifications, the reflective scanning method can be used on EBT3 as an economic alternative to the transmission method which was also one of the goals of this study. A comparison is also done between single scan configuration including all samples in a single A4 (HP) or A3 (EPSON) format area and multiple scan procedure where each sample is scanned separately on its own. The images analyses are done using the ImageJ software. Results show significant influence of the scanning configuration but no significant differences between electron and photon irradiations for both single and multiple scan configurations. In conclusion, the film provides a reliable relative dose measurement method for electrons and photons irradiations in the medical field applications.     

The relative biological effectiveness of low doses of 14 MeV neutrons in steady-state murine spermatogenesis as determined by flow cytometry

The relative biological effectiveness of 14 MeV neutrons in the low-dose range < or =1 Gy has been determined in differentiating and differentiated spermatogonia. Male NMRI mice were exposed to single doses of 2 cGy to 3 Gy of (60)Co gamma rays or neutrons. The ratios of testicular S-phase cells, 4c primary spermatocytes, and elongated spermatids were quantified by DNA flow cytometry 2 to 70 days after irradiation and were found to decrease. Histological samples and testis weight were analyzed in parallel. Doses of 2-5 cGy neutrons and 10-50 cGy gamma rays significantly (P<0.05) decreased the proportions of S-phase cells, spermatocytes and elongated spermatids at 4, 14 and 28 days postirradiation. For S-phase cells, the biphasic shape of the cell survival curves was described with a D(50) of 5 cGy neutrons. The D(50) for (60)Co gamma rays and the relative biological effectiveness could not be determined. The relative biological effectiveness of neutrons at 50% reductions of testis weight, primary spermatocytes, and elongated spermatids were 2.5, 10.0 and 6.1, respectively. This in vivo assay is interesting because of its sensitivity at dose ranges that are relevant for exposures in the environment, the workplace and radiotherapy.     

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.     

Effects of electrons and neutrons on the synthesis of RNA in resistant and sensitive strains of the slime-mould Dictyostelium discoideum and the modifying effect of caffeine.

RNA synthesis was investigated after irradiation in resistant and sensitive lines of the slime-mould Dictyostelium discoideum. When 3H adenine was used as a precursor to RNA, incorporation increased after irradiation in the resistant WT line but not in the sensitive line (gammas-13). The extent of RNA synthesis after irradiation was correlated with the shoulder width on the survival curve of the resistant line. When this was reduced by irradiating with neutrons, or treatment with caffeine RNA synthesis was also reduced. No preferential synthesis of one RNA species occurred; there was increased labelling in all RNA species after irradiation. Sucrose gradient analysis of ribosomal RNA extracted from irradiated cells and free of messenger RNA revealed no apparent difference in composition from that extracted from unirradiated cells. Increased RNA synthesis after irradiation may form part of the recovery processin the resistant cells.