The effectiveness of monoenergetic neutrons at 565 keV in producing dicentric chromosomes in human lymphocytes at low doses

The induction of dicentric chromosomes in human lymphocytes from one individual irradiated in vitro with monoenergetic neutrons at 565 keV was examined to provide additional data for an improved evaluation of neutrons with respect to radiation risk in radioprotection. The resulting linear dose-response relationship obtained (0.813 +/- 0.052 dicentrics per cell per gray) over the dose range of 0.0213-0.167 Gy is consistent with published results obtained for irradiation with neutrons from different sources and with different spectra at energies lower than 1000 keV. Comparing this value to previously published "average" dose-response curves obtained by different laboratories for (60)Co gamma rays and orthovoltage X rays resulted in maximum RBEs (RBE(m)) of about 37 +/- 8 and 16 +/- 4, respectively. However, when our neutron data were matched to low-LET dose responses that were constructed several years earlier for lymphocytes from the same individual, higher values of RBE(m) resulted: 76.0 +/- 29.5 for (60)Co gamma rays and 54.2 +/- 18.4 for (137)Cs gamma rays; differentially filtered 220 kV X rays produced values of RBE(m) between 20.3 +/- 2.0 or 37.0 +/- 7. 1. The results highlight the dependence of RBE(m) on the choice of low-LET reference radiation and raise the possibility that differential individual response to low-LET radiations may need to be examined more fully in this context.     

A radiobiological model for the relative biological effectiveness of high-dose-rate 252Cf brachytherapy

While there is significant clinical experience using both low- and high-dose-rate 252Cf brachytherapy, there are minimal data regarding values for the neutron relative biological effectiveness (RBE) with both modalities. The aim of this research was to derive a radiobiological model for 252Cf neutron RBE and to compare these results with neutron RBE values used clinically in Russia. The linear-quadratic (LQ) model was used as the basis to characterize cell survival after irradiation, with identical cell killing rates (S(N) = S(gamma)) between 252Cf neutrons and photons used for derivation of RBE. Using this equality, a relationship among neutron dose and LQ radiobiological parameter (i.e., alpha(N), beta(N), alpha(gamma), beta(gamma)) was obtained without the need to specify the photon dose. These results were used to derive the 252Cf neutron RBE, which was then compared with Russian neutron RBE values. The 252Cf neutron RBE was determined after incorporating the LQ radiobiological parameters obtained from cell survival studies with fast neutrons and teletherapy photons. For single-fraction high-dose-rate neutron doses of 0.5, 1.0, 1.5 and 2.0 Gy, the total biologically equivalent doses were 1.8, 3.4, 4.7 and 6.0 RBE Gy with 252Cf neutron RBE values of 3.2, 2.9, 2.7 and 2.5, respectively. Using clinical data for late-responding reactions from 252Cf, Russian investigators created an empirical model that predicted high-dose-rate 252Cf neutron RBE values ranging from 3.6 to 2.9 for similar doses and fractionation schemes and observed that 252Cf neutron RBE increases with the number of treatment fractions. Using these relationships, our results were in general concordance with high-dose-rate 252Cf RBE values obtained from Russian clinical experience.     

The effect of 29 kV X rays on the dose response of chromosome aberrations in human lymphocytes

The induction of chromosome aberrations in human lymphocytes irradiated in vitro with X rays generated at a tube voltage of 29 kV was examined to assess the maximum low-dose RBE (RBE(M)) relative to higher-energy X rays or 60Co gamma rays. Since blood was taken from the same male donor whose blood had been used for previous irradiation experiments using widely varying photon energies, the greatest possible accuracy was available for such an estimation of the RBE(M), avoiding the interindividual variations in sensitivity or differences in methodology usually associated with interlaboratory comparisons. The magnitude of the linear coefficient alpha of the linear-quadratic dose-effect relationship obtained for the production of dicentric chromosomes by 29 kV X rays (alpha = 0.0655 +/- 0.0097 Gy(-1)) confirms earlier observations of a strong increase in alpha with decreasing photon energy. Relating this value to previously published values of alpha for the dose-effect curves for dicentrics obtained in our own laboratory, RBE(M) values of 1.6 +/- 0.3 in comparison with weakly filtered 220 kV X rays, 3.0 +/- 0.7 compared to heavily filtered 220 kV X rays, and 6.1 +/- 2.5 compared to 60Co gamma rays have been obtained. These data emphasize that the choice of the reference radiation is of fundamental importance for the RBE(M) obtained. A special survey of the RBE(M) values obtained by different investigators in the narrow quality range from about 30 to 350 kV X rays indicates that the present RBE is in fairly good agreement with previously published findings for the induction of chromosome aberrations or micronuclei in human lymphocytes but differs from recently published findings for neoplastic transformation in a human hybrid cell line.     

Neutron RBEs for mouse skin at low doses per fraction

The effect of low doses of 240 kVp X rays or of 3 MeV neutrons has been investigated using skin reactions on mouse feet as the biological system. Eight or nine repeated small doses of radiation were used, followed by graded "top-up" doses to bring the reactions into a detectable range. By comparing dose-response curves, the RBE has been determined for neutron doses per fraction ranging from 0.25-1.0 Gy. The data are consistent with a limiting RBE of between 7 and 10 at very low doses. A review of other published RBE values for low doses per fraction shows a wide range of RBEs . Very few studies show a plateau value for the RBE. These findings are more consistent with dose-response data that fit a linear-quadratic model than with a multitarget single-hit model.     

The maximum low-dose RBE of 17.4 and 40 keV monochromatic X rays for the induction of dicentric chromosomes in human peripheral lymphocytes

Schmid et al. recently reported on the maximum low-dose RBE for mammography X rays (29 kV) for the induction of dicentrics in human lymphocytes. To obtain additional information on the RBE for this radiation quality, experiments with monochromatized synchrotron radiation were performed. Monochromatic 17.4 keV X rays were chosen for comparison with the diagnostic mammography X-ray spectrum to evaluate the spectral influence, while monochromatic 40 keV X rays represent a higher-energy reference radiation, within the experiment. The induction of dicentric chromosomes in human lymphocytes from one blood donor irradiated in vitro with 17.4 keV and 40 keV monochromatic X rays resulted in alpha coefficients of (3.44 +/- 0.87) x 10(-2) Gy(-1) and (2.37 +/- 0.93) x 10(-2) Gy(-1), respectively. These biological effects are only about half of the alpha coefficients reported earlier for exposure of blood from the same donor with the broad energy spectra of 29 kV X rays (mean energy of 17.4 keV) and 60 kV X rays (mean energy of 48 keV). A similar behavior is evident in terms of RBEM. Relative to weakly filtered 220 kV X rays, the RBEM for 17.4 and 40 keV monochromatic X rays is 0.86 +/- 0.23 and 0.59 +/- 0.24, respectively, which is in contrast to the RBEM of 1.64 +/- 0.27 for 29 kV X rays and 1.10 +/- 0.19 for 60 kV X rays. It is evident that the monochromatic radiations are less effective in inducing dicentric chromosomes than broad-spectrum X rays with the corresponding mean energy value. Therefore, it can be assumed that, for these X-ray qualities with broad energy spectra, a large fraction of the effects should be attributed predominantly to photons with energies well below the mean energy.     

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.     

Induction of chromosome aberrations in G0 human lymphocytes by low doses of ionizing radiations of different quality

Human peripheral blood lymphocytes from two donors were exposed to low doses (0.05 to 2.0 Gy) of gamma rays, X rays, or fast neutrons of different energies. Chromosome aberrations were analyzed in metaphase of first-division cells after a culture time of 45-46 hr. At this time, less than 5% of the cells were found in second division. Different dose-response relationships were fitted to the data by using a maximum likelihood method; best fits for radiation-induced dicentric aberrations were obtained with the linear-quadratic law for all radiations. The linear component of this equation predominated, however, for neutrons in the range of doses studied, and the frequency of dicentrics induced by d(16)+Be neutrons up to 1.0 Gy could also be described by a linear relationship. The relative biological efficiency (RBE) of X rays and d(16)+Be, d(33)+Be, and d(50)+Be neutrons compared to 60Co gamma rays in the low dose range was calculated from the dose-effect relationships for the dicentrics produced. The RBE increased with decreasing neutron dose and with decreasing neutron energy from d(50)+Be to d(16)-+Be neutrons. The limiting RBE at low doses (RBEo) was calculated to be about 1.5 for X rays and 14.0, 6.2, and 4.7 for the d(16)+Be, d(33)+Be, and d(50)+Be neutrons, respectively.     

Occurrence of mammary tumors in rats after exposure to tritium beta rays and 200-kVp X rays

The RBE for tritium was estimated in reference to 200-kVp X rays, using acceleration of breast tumor appearance in the female Sprague-Dawley rat as the end-point. Chronic X-ray doses of 0.3-2.0 Gy were delivered over 10 days. Intraperitoneal injections of tritiated water ranging in concentrations from 45 to 370 MBq/100 g body wt were administered, followed by four additional injections at 2-day intervals and half of the initial concentrations. Seventy-five percent of the total tritium dose was delivered to the mammary gland within the first 10 days and 95% within the first 20 days after the start of the tritium exposure. RBE estimations were based on various criteria including the tumor incidence per Gy at 450 days postirradiation and the time required to induce tumors in 50% of the animals at risk. The results suggest that tritium beta rays are about 1.1-1.3 times more effective than chronic 200-kVp X rays for acceleration of the appearance of rat mammary tumors. However, the uncertainties involved in these calculations are such that the effects of tritium beta rays could not be reliably distinguished from those of chronic 200-kVp X rays. Measured differences in RBE values were slightly larger for the comparison between acute and chronic X rays than for the comparison between chronic tritium beta rays and chronic X rays.     

Life shortening and disease incidence in BALB/c mice following a single d(50)-Be neutron or gamma exposure

Male BALB/c mice, 12 weeks old, were given a single exposure of either 137Cs gamma rays or d(50)-Be neutrons at a dose rate of 3 Gy/min. The animals were kept until death, and causes of death or possible causes of death were ascertained by autopsy and histology. The data were evaluated by competing risk methods. The survival time dose-effect curve for both types of exposure was linear and did not differ significantly (slopes: 55.8 +/- 4.0 days/Gy for neutrons and 46.2 +/- 4.3 days/Gy for gamma rays). The incidence of different diseases also was similar for both groups except that more carcinomas, sarcomas, and myeloid leukemias seemed to occur after neutron exposure and that nonstochastic lung and kidney diseases seemed to arise at lower doses.     

A test of equal effect per fraction in the kidney of the mouse.

Measurements of renal damage in the mouse were made to determine if there was an equal effect per fraction during a course of repeated 240-kVp X-ray doses. An X-ray dose of 2 Gy was given 2, 8, 14, or 20 times with interfraction intervals of 12 h. Some animals were also irradiated with twenty 2-Gy doses using a 5-h interfraction interval. The underlying effect per fraction (-logeSF of the notional target cell population) was determined from the additional top-up dose of d(4)-Be neutrons needed to produce measurable renal impairment assessed by decreased clearance from the plasma of [51Cr]EDTA and by a reduction in the hematocrit at 25, 29, 33, and 39 weeks after treatment. There was no significant influence of the time of assay on the values of underlying effect measured. A mean value of underlying effect was therefore calculated for the two different assays of each mouse, from the measurements at the four times. This gave approximately 40 estimates (one for each animal assessed) with each assay of the effectiveness of 2-Gy fractions in each of the four fractionation schedules, a total of 321 determinations in the study with 12-h intervals. Regression analysis showed that there was no significant trend in underlying effect per fraction with number of fractions, i.e., the damage per fraction was constant regardless of the number of fractions used. With underlying effect normalized to 1 unit of damage for a single 2-Gy dose, the slope of this plot was -0.0013 per fraction2 +/- 0.0097 (95% CL). The assumption of equal effect per fraction was therefore not invalidated in the kidney of the mouse. With a 5- instead of a 12-h interfraction interval, the 20-fraction schedule was 7% more effective as measured by the two assays analyzed together; this was significant at P = 0.0001. This shows that 5 h is not sufficient time between fractions for full repair to occur in the kidney, and underlines the need for intervals of at least 6 h between the doses in clinical radiotherapy using more than one fraction per day. The data are consistent with an alpha/beta ratio approximately 1.6 Gy, with a repair half-time approximately 1.3 h. However, these experiments were not designed to determine these parameters and their values should be regarded only as rough estimates.     

RBE of X rays of different energies: a cytogenetic evaluation by FISH

Mammography using 26-30 kVp X rays is routinely used in breast cancer screening. Discussion about the radiation-related risk associated with this methodology is ongoing. For radioprotection purposes, a quality factor of 1 has been assigned for all photon energies. However, the relative biological effectiveness (RBE) could increase as the photon energy decreases. Analyzing different biological parameters, for 30 kVp X rays, RBE values from 1 to 8 have been estimated. In the present study, a cytogenetic FISH evaluation of the RBE of 30, 80 and 120 kVp X rays has been done. Blood samples were irradiated with 10 doses from 0.05 to 3 Gy for each energy studied. The yields of translocations and dicentrics were determined by fluorescence in situ hybridization (FISH) using whole chromosome probes for chromosomes 1, 4 and 11 together with a pancentromeric probe. The alpha coefficients of the dose-effect curves for dicentrics, minimum number of breaks needed to produce exchange-type aberrations, and apparently simple translocations were used to estimate the RBE. Using the curves obtained for 120 kVp as a reference, the RBE values for dicentrics were 1.08+/-0.43 and 1.73+/-0.59 for 80 and 30 kVp X rays, respectively; for minimum number of breaks these values were 1.38+/-0.39 and 1.42+/-0.41, and for apparently simple translocations they were 1.26+/-0.40 and 1.51+/-0.47, respectively. Moreover, the induction of complex aberrations by these energies was compared. The percentage of complex aberrations relative to total aberrations showed a significant tendency to increase as X-ray energy decreased: 7.8+/-1.19, 9.8+/-1.6 and 14.1+/-1.9 for 120, 80 and 30 kVp, respectively (P<0.02).     

Lung tumour induction in mice after X-rays and neutrons

Dose-response curves were determined for pulmonary adenomas and adenocarcinomas in mice after single acute doses of 200 kVp X-rays and cyclotron neutrons (E = 7.5 MeV). A serial-killing experiment established that the radiation induces the tumours and does not merely accelerate the appearance of spontanoeus cancers [corrected]. The dose versus incidence (I) of tumours in male and female mice for X-ray doses between 0.25 and 7.5 Gy is 'bell-shaped' and best fitted with a purely quadratic induction and exponential inactivation terms, i.e. I = A + BD2e-alpha D. In contrast, the tumour dose-response after 0.1-4.0 Gy of neutrons is best fitted by I = A + BDe-alpha D and is steeply linear less than or equal to 1 Gy, peaks between 1 and 3 Gy and sharply declines at 4.0 Gy. The data for the female mice less than or equal to 1 Gy neutrons are best fitted to the square root of the dose. A major objective of the experiments was to derive neutron RBE values. Because of the differences between the X-ray (quadratic) and neutron (linear) curves, the RBEn will vary inversely with decreasing X-ray dose. The RBE values at 1 Gy of X-rays derived from the B coefficients in the above equations are 7.4 +/- 3.2 (male and female); 8.6 +/- 3.6 (female) and 4.7 +/- 1.8 (male). These are high values and imply even higher values at the doses of interest to radiation protection. If, however, one restricts the analysis to the initial, induction side of the response (less than or equal to 1 Gy neutrons, less than or equal to 3 Gy X-rays) then good linear fits are obtainable for both radiations and indicate neutron RBE values of 7.4 +/- 2.3 for female mice and 4.5 +/- 1.8 for males, and these are independent of dose level.     

Lung cancer risk in mice: analysis of fractionation effects and neutron RBE with a biologically motivated model

Data from Argonne National Laboratory on lung cancer in 15,975 mice with acute and fractionated exposures to gamma rays and neutrons are analyzed with a biologically motivated model with two rate-limiting steps and clonal expansion. Fractionation effects and effects of radiation quality can be explained well by the estimated kinetic parameters. Both an initiating and a promoting action of neutrons and gamma rays are suggested. While for gamma rays the initiating event is described well with a linear dose-rate dependence, for neutrons a nonlinear term is needed, with less effectiveness at higher dose rates. For the initiating event, the neutron RBE compared to gamma rays is about 10 when the dose rate during each fraction is low. For higher dose rates this RBE decreases strongly. The estimated lifetime relative risk for radiation-induced lung cancers from 1 Gy of acute gamma-ray exposure at an age of 110 days is 1.27 for male mice and 1.53 for female mice. For doses less than 1 Gy, the effectiveness of fractionated exposure to gamma rays compared to acute exposure is between 0.4 and 0.7 in both sexes. For lifetime relative risk, the RBE from acute neutrons at low doses is estimated at about 10 relative to acute gamma-ray exposure. It decreases strongly with dose. For fractionated neutrons, it is lower, down to about 4 for male mice.     

Biological effectiveness of neutrons from Hiroshima bomb replica: results of a collaborative cytogenetic study

The effectiveness of neutrons from a facsimile of the Hiroshima bomb was determined cytogenetically. The "Little-Boy" replica (LBR), assembled at Los Alamos as a controlled nuclear reactor for detailed physical dosimetry, was used. Of special interest, the neutron energy characteristics (including lineal energy) measured 0.74 m from the LBR were remarkably similar to those calculated for the 1945 Hiroshima bomb at 1 to 2 km from the hypocenter, as shown in a companion dosimetric paper (Straume, et al., Radiat. Res. 128, 133-142 (1991)). Thus we examine here the effectiveness of neutrons closely resembling those that the A-bomb survivors received at Hiroshima. Chromosome aberration frequencies were determined in human blood lymphocytes exposed in vitro to graded doses of LBR radiation (97% neutrons, 3% gamma rays). Vials of blood suspended in air at distances up to 2.10 m from the center of the LBR uranium core received doses ranging from 0.02 to 2.92 Gy. The LBR neutrons (E approximately 0.2 MeV) produced 1.18 dicentrics and rings per cell per Gy. They were more effective than the higher-energy fission neutrons (E approximately 1 MeV) commonly used in radiobiology. The maximum RBE (RBEM) of LBR neutrons at low doses is estimated to be 60 to 80 compared to 60Co gamma rays and 22 to 30 compared to 250-kVp X rays. These results provide a quantitative measurement of the biological effectiveness of Hiroshima-like neutrons.     

Nonlinear survival curves for cells of solid tumors after large doses of fast neutrons and gamma rays.

We have previously proposed that survival curves for cells of murine NFSa fibrosarcomas after exposure to fast neutrons might demonstrate curvature when the neutron doses reach a level high enough to cure the fibrosarcomas. We report here that this is the case. Murine NFSa fibrosarcomas growing in the hind legs of syngeneic mice were exposed to either gamma rays or fast neutrons. The tumors were removed and retransplanted into fresh recipients to obtain 50% tumor cell doses, from which the dose-cell survival relationship was constructed. Survival curves showed continuous bending down to 10(-7), and were well fitted using the linear-quadratic model. The alpha and beta values for neutrons were larger than those for gamma rays. When the surviving fractions at experimental TCD50 doses were calculated using these values, comparable figures were obtained for neutrons and gamma rays. The RBEs for neutrons were comparable for the TCD50 and TD50 assays. Neutron RBE was independent of dose within a range of 5-28 Gy. The capacity of the tumors to repair the damage caused by large doses of neutrons was identical to that for small doses of neutrons, indicating that cells retained the capacity to repair neutron damage irrespective of the size of the dose.     

RBE of 10 kV X rays determined for the human mammary epithelial cell line MCF-12A

The dependence of relative biological effectiveness (RBE) on photon energy is a topic of extensive discussions. The increasing amount of in vitro data in the low-energy region indicates this to be a complex dependence that is influenced by the end point and cell line studied. In the present investigation, the RBE of 10 kV X rays (W anode) was determined relative to 200 kV X rays (W anode, 0.5 mm copper filter) for cell survival in the dose range 1-10 Gy and for induction of micronuclei in the range 0.5-3.6 Gy for MCF-12A human mammary epithelial cells. The RBE for cell survival was found to increase with decreasing dose, being 1.21+/-0.03 at 10% survival. Considerably higher values were obtained for micronucleus induction, where the RBE(M) obtained from the ratio of the linear coefficients of the dose-effect curves was 2.6+/-0.4 for the fraction of binucleated cells with micronuclei and 4.1+/-1.0 for the number of micronuclei per binucleated cell. These values, together with our previous data, support a monotonic increase in RBE with decreasing photon energy down to the mean energy of 7.3 keV used in the present study.     

Accelerated heavy particles and the lens. VI. RBE studies at low doses

We report on the prevalence, hazard, and relative biological effectiveness (RBE) for various stages of lens opacification in rats induced by very low doses of fast argon ions of LET 88 keV/microns, compared to those for X rays. Doses of argon ions from 0.01 to 0.25 Gy were used and RBEs of these ions relative to X rays estimated using a nonparametric technique. At the end of the follow-up period, which encompasses a significant fraction of the animals' lifetime, 90% confidence intervals for the RBE of the argon ions relative to X rays were 4-8 at 0.25 Gy, 10-40 at 0.05 Gy, and 50-100 at 0.01 Gy. Our results are consistent with the point-estimate neutron RBEs in Japanese A-bomb survivors, though broad confidence bounds are present in the Japanese results. If a reasonable extrapolation to higher doses is used, our results are also consistent with data reported earlier at higher doses for argon-ion cataractogenesis in rats, mice, and rabbits. We conclude from these results that at very low doses the RBE for cataractogenesis from HZE particles in space is considerably more than 20, and use of a quality factor of at least 50 would be prudent.     

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.     

Relative biological effectiveness and tolerance dose of fission neutrons in canine skin for a potential combination of neutron capture therapy and fast-neutron therapy

To investigate the potential efficacy of fission neutrons from a fast-neutron reactor for the treatment of radioresistant tumors, the relative biological effectiveness (RBE) and tolerance dose of fission neutrons in canine skin were determined. The forelimbs of 34 healthy mongrel dogs received a single dose of fission neutrons (5.6, 6.8, 8.2, 9.6 or 11 Gy) or 137Cs gamma rays (10, 15, 20, 25 or 30 Gy). Based on observations of radiodermatitis for each radiation, the single-fraction RBE of fission neutrons in the sixth month was calculated as approximately 3. The tolerance doses of fission neutrons and gamma rays, defined as the highest doses giving no moist desquamation on the irradiated skin in the recovery phase, were estimated as 7.6 Gy and 20 Gy, respectively. The tolerance dose of 7.6 Gy of fission neutrons included 5.0 Gy of fast neutrons possessing high anti-tumor effects and 1.4 x 10(12) n/cm2 of thermal neutrons, which could be applicable to neutron capture therapy (NCT). The combination of fast-neutron therapy and NCT using a fast-neutron reactor might be useful for the treatment of radioresistant tumors.