Neutron Relative Biological Effectiveness Research Articles

A Radiobiological Model for the Relative Biological Effectiveness of High-Dose-Rate252Cf 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.

MO-D-T-6E-08: Derivation of the Relative Biological Effectiveness of High Dose Rate 252Cf Brachytherapy

Purpose: While there is significant clinical experience using both low- and high-dose rate (HDR) brachytherapy, there is 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 neutron RBE and to compare these results with neutron RBE values used clinically in Russia. Method and Materials: The linear-quadratic (L-Q) model was used as the basis to characterize cell survival following irradiation, with identical cell killing rates (SN = Sγ) between neutrons and photons used for derivation of RBE. Using this equality, a relationship among neutron dose and L-Q radiobiological parameter (i.e., αN, βN, αγ, βγ) was obtained without need to specify the photon dose. These results were used to derive the neutron RBE which was then compared with Russian neutron RBE values. The neutron RBE was determined after incorporating the L-Q radiobiological parameters obtained from cell survival studies with fast neutrons and teletherapy photons. Results: For single-fraction HDR neutron doses of 0.5, 1.0, and 1.5 Gy, the total (neutron plus photon) doses were 3.5, 6.0, and 8.1 Gy, with neutron RBE values of 6.4, 5.5, and 4.9, respectively. Russian clinicians obtained HDR neutron RBE values ranging from 7 to 3 for similar doses and fractionation schemes, and observed that neutron RBE increases with the number of fractions and is dose rate dependent. A value of 5 was obtained for HDR neutron RBE. Conclusion: The methodology presented herein presents a reasonable technique to utilize well-characterized radiobiology parameters from radiation sources having similar radiobiological properties towards obtaining calculated values for RBE. Using these relationships, results were in general concordance with RBE values obtained from Russian clinical experience.

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.

Energy-dependent RBE of Neutrons to Induce Micronuclei in Root-tip Cells of Allium cepa Onion Irradiated as Dry Dormant Seeds and Seedlings.

The relative biological effectiveness (RBE) of various energy neutrons produced from a Schenkel-type accelerator at the Research Institute for Radiation Biology and Medicine, Hiroshima University (HIRRAC), compared with 60Co gamma-ray radiation was determined. The neutron radiations and gamma-ray radiation produced good linear changes in the frequency of micronuclei induced in the root-tip cells of Allium cepa onion irradiated as dry dormant seeds (seed assay) and seedlings (seedling assay) with varying radiation doses. Therefore the RBE for radiation-induced micronuclei can be calculated as the ratio of the slopes of the fitted linear dose response for the neutron radiations and the 60Co gamma-ray radiation. The RBE values by seed assay and seedling assay decreased to 174 +/- 7, from 216 +/- 9, and to 31.4 +/- 1.0, from 45.3 +/- 1.3 (one standard error), respectively, when neutron energies increased to 1.0 MeV, from 0.2 MeV, in the present study. Furthermore, the ratio of the micronucleus induction rates of seed assay to seedling assay by gamma-ray radiation was much lower than that by neutron radiations.

Analysis of breast cancer in the Massachusetts TB fluoroscopy cohort and in the Japanese A-bomb survivors, taking account of dosimetric error and curvature in the A-bomb dose response: absence of evidence of reduction of risk following fractionated irrad

Breast cancer has occurred in excess among women exposed briefly to atomic bomb radiation and among those exposed repeatedly over many years to medical radiation for tuberculosis (TB). The breast cancer excess is strongly dependent on age at exposure, with risk highest among the young and small or non-existent when exposure occurs past the menopausal ages. The linear excess relative risk coefficient of breast cancer incidence in the Japanese A-bomb survivor data, however, is significantly higher (two-sided P = 0.04) than that in the Massachusetts TB fluoroscopy data; this remains the case (two-sided P = 0.03) if account is also taken of possible curvature in the A-bomb survivor dose response and random dosimetric errors. The best estimate of the ratio between the linear excess relative risk coefficients for the Japanese and Massachusetts cohorts is 2.11 (95% CI 1.05, 4.95), or 3.18 (95% CI 1.19, 8.21) if account is taken of dosimetric error and possible curvature in the A-bomb survivor data. However, this higher relative excess risk is attributable to the lower baseline risk of breast cancer among Japanese compared with the Massachusetts women, and the linear excess absolute breast cancer risk coefficients in the two data sets are statistically indistinguishable (two-sided P = 0.32). The best estimate of the ratio between the excess absolute risk coefficients among Japanese and Massachusetts women is 0.73 (95% CI 0.41, 1.44). Again, if account is also taken of possible curvature in the A-bomb survivor dose response and random dosimetric errors, these results are not substantially altered; in this case the best estimate of the ratio between the linear excess absolute risk coefficients among Japanese and Massachusetts women is 1.07 (95% CI 0.42, 2.38) (two-sided P = 0.86). These results are not sensitive to the assumed neutron relative biological effectiveness for the Japanese data, or analyses over restricted dose ranges in this data set. In general, there are no marked differences between the Massachusetts and Japanese data sets in the age and time distribution of risk of radiation-induced breast cancer. These data provide little evidence for a reduction in breast cancer risk following fractionated irradiation.

344. Radiobiological supplying of oncological patient radial therapy

The examination of radiobiological peculiarities of therapeutic ionizing radiation source action gives an opportunity of preferable choice of exposure requirements of the oncological patients. The therapeutic ionizing radiation source, inlet into operation, should pass radiobiological examination, including with the purpose of definition of relative biological effectiveness (RBE) depending on quality, radiation dose, radiosensitiveness of cells etc. The cytogenetic dosimetry is carried out at an exposure of man Iymphocyte culture the on therapeutic source 137Cs, 60Co, neutrons with average energy 6 and 22 MeV. Is shown that isoeffective distribution of the neutron energy does not correspond with physical isodose distribution allowing for RBE constant value. For the first time is shown that for optimization of patient exposure therapeutic effect rationally to use neutron RBE variable values. For the first time is shown that RBE value of 137Cs gamma-quantum used for intracavitary radiotherapy, exceed 1 (in comparison with 60Co) and in dose range 0,15 – 5,0 Gy makes 3,5 – 1,2 accordingly. The method of approximating of association “dose - effect” on basis of spline regression which is characterized by smaller values of model parameter errors for various cytogenetic indexs and enables to forecast effect of calibrating curve outlet on a plateau is designed and proposed. The dose curves for RBE definition of therapeutic ionizing radiation source on the basis of spline regression model have to be taken into consideration for decrease of frequency and expressiveness of radiocomplications at an oncological patient exposure.

The impact of possible modifications to the DS86 dosimetry on neutron risk andrelative biological effectiveness

The current DS86 dosimetry system for the Japanese bomb survivors indicatesthat neutron doses were so low that they prevent the direct derivation of anyuseful estimates of neutron risk. However, the large body of thermal neutronactivation measurements carried out over many years in Hiroshima and Nagasakiappear to indicate that current DS86 neutron doses may have been significantlyunderestimated in Hiroshima. An earlier companion paper has provided an updateof neutron activation measurements. While a large body of data appears tosupport a significant increase, there is ongoing debate and review regarding itsvalidity. However, as yet, there are no detailed, peer-reviewed, publishedrefutations of the neutron activation data which appear to support an increase inneutron doses. In this paper, we consider the impact of possible futurerevisions in the DS86 dosimetry on radiation risk estimates. We considerthe extreme range of possibilities from maintaining the existing DS86values, to changes in neutron doses in accord with the majority of existingneutron activation data. We have used the latest cancer incidence dataand cancer mortality data for the A-bomb survivors, and neutron doseshave been modified using a neutron revision factor (NRF) in line withthe latest thermal neutron activation measurements in Hiroshima. Incontrast to previous analyses, a nonlinear relationship between log(NRF)and slant range has been used which better represents the data beyondslant ranges of ∼1 km. The impact on the evaluation of neutron relativebiological effectiveness (RBE) and gamma radiation risk estimates has beenassessed. While DS86 neutron doses are too low to allow any useful directevaluation of neutron risk or neutron RBE, it becomes possible to derive moremeaningful values if neutron doses are increased in Hiroshima in linewith the broad range of thermal neutron activation measurements. Theuncertainties are smallest for the cancer incidence data. The best estimates ofneutron RBE give upper 95% confidence limits of about 6 for all solidtumours for the incidence data and about 28 for the mortality data. Theuncertainties in neutron RBE for leukaemia incidence are larger, andestimation at doses below about 0.1 Gy is not possible. There is no significantchange in the excess relative risk for gamma radiation for all solid tumourstaken together, compared with the current DS86 dosimetry. The resultspreclude neutron RBE values significantly greater than the current ICRPradiation weighting factors, which range between 5 and 20, depending onenergy. Whether or not the Japanese bomb survivors can indeed form thebasis for useful, directly determined neutron risks clearly depends on theveracity of existing neutron activation data. This is currently the subjectof careful international scrutiny and the outcome is eagerly awaited.

Impact of the p53 status of the tumor cells on the effect of reactor neutron beam irradiation, with emphasis on the response of intratumor quiescent cells.

Human head and neck squamous cell carcinoma cells transfected with mutant p53 (SAS/mp53) or with neo vector as a control (SAS/neo) were inoculated subcutaneously into both the hind legs of Balb/cA nude mice. Tumor‐bearing mice received 5‐bromo‐2′‐deoxyuridine (BrdU) continuously to label all proliferating (P) cells in the tumors. After administration of sodium borocaptate‐10B (BSH) or p‐boronophenylalanine‐10B (BPA), the tumors were irradiated with neutron beams. The tumors not treated with 10B‐compound were irradiated with neutron beams or γ‐rays. The tumors were then excised, minced and trypsinized. The tumor cell suspensions thus obtained were incubated with a cytokinesis blocker, and the micronucleus (MN) frequency in cells without BrdU labeling (=quiescent (Q) cells) was determined using immunofluorescence staining for BrdU. Meanwhile, 6 h after irradiation, tumor cell suspensions obtained in the same manner were used for determining the frequency of apoptosis in Q cells. The MN and apoptosis frequencies in total (P+Q) tumor cells were determined from the tumors that were not pretreated with BrdU. Without 10B‐carriers, in both tumors, the relative biological effectiveness of neutrons was greater in Q cells than in total cells, and larger for low than high cadmium ratio neutrons. With 10B‐carriers, the sensitivity was increased for each cell population, especially for total cells. BPA increased both frequencies for total cells more than BSH. Nevertheless, the sensitivity of Q cells treated with BPA was lower than that of BSH‐treated Q cells. These sensitization patterns in combination with 10B‐carriers were clearer in SAS/neo than in SAS/mp53 tumors. The p53 status of the tumor cells had the potential to affect the response to reactor neutron beam irradiation following 10B‐carrier administration.

Risk Estimation for Fast Neutrons with Regard to Solid Cancer

In the absence of epidemiological information on the effects of neutrons, their cancer mortality risk coefficient is currently taken as the product of two low-dose extrapolations: the nominal risk coefficient for photons and the presumed maximum relative biological effectiveness of neutrons. This approach is unnecessary. Since linearity in dose is assumed for neutrons at low to moderate effect levels, the risk coefficient can be derived in terms of the excess risk from epidemiological observations at an intermediate dose of gamma rays and an assumed value, R(1), of the neutron RBE relative to this reference dose of gamma rays. Application of this procedure to the A-bomb data requires accounting for the effect of the neutron dose component, which, according to the current dosimetry system, DS86, amounts on average to 11 mGy in the two cities at a total dose of 1 Gy. With R(1) tentatively set to 20 or 50, it is concluded that the neutrons have caused 18% or 35%, respectively, of the total effect at 1 Gy. The excess relative risk (ERR) for neutrons then lies between 8 per Gy and 16 per Gy. Translating these values into risk coefficients in terms of the effective dose, E, requires accounting for the gamma-ray component produced by the neutron field in the human body, which will require a separate analysis. The risk estimate for neutrons will remain essentially unaffected by the current reassessment of the neutron doses in Hiroshima, because the doses are unlikely to change much at the reference dose of 1 Gy.

City-effects in the atomic bomb survivors data

It was investigated how risk estimates derived from the RERF life span study data sets for cancer incidence and mortality, respectively, differ between the two cities Hiroshima and Nagasaki, and the two sexes. This was done by estimating the excess risk for various age-at-exposure and time-since-exposure groups. The epidemiologically most reliable age group are those aged 20–39 years at the time of exposure. As expected, in this group, the relative risk for females in Hiroshima is higher than that for males; however, in Nagasaki, the relative risk for females is lower than that for males. When comparing the risks in the two cities for the same sex, the risks of cancer incidence and mortality of females exposed in Hiroshima are higher than those in Nagasaki. However, for the males, the risks of cancer incidence in Hiroshima are lower than in Nagasaki, and the risks of cancer mortality of males are very similar between both cities. All differences depend on age-at-exposure and time-since-exposure, and are at the borderline of being statistically significant. The absorbed dose of neutrons, for the same γ-dose, is about three times as high in Hiroshima than in Nagasaki for both sexes. Because of these observed risk differences between both cities, it does not appear to be possible to reliably estimate the relative biological effectiveness of neutrons as compared to that of γ-rays from these epidemiological data sets. No evidence was found in this analysis that the radiation weighting factors w R presently used for neutrons in radiation protection could severely underestimate the risks for somatic late effects induced by neutrons.

Effects of low-dose neutrons applied at reduced dose rate on human melanoma cells.

Human melanoma cells that are resistant to gamma rays were irradiated with 14 MeV neutrons given at low doses ranging from 5 cGy to 1.12 Gy at a very low dose rate of 0.8 mGy min(-1) or a moderate dose rate of 40 mGy min(-1). The biological effects of neutrons were studied by two different methods: a cell survival assay after a 14-day incubation and an analysis of chromosomal aberrations in metaphases collected 20 h after irradiation. Unusual features of the survival curve at very low dose rate were a marked increase in cell killing at 5 cGy followed by a plateau for survival from 10 to 32.5 cGy. The levels of induced chromosomal aberrations showed a similar increase for both dose rates at 7.5 cGy and the existence of a plateau at the very low dose rate from 15 to 30 cGy. The existence of a plateau suggests that a repair process after low-dose neutrons might be induced after a threshold dose of 5-7.5 cGy which compensates for induced damage from doses as high as 32.5 cGy. These findings may be of interest for understanding the relative biological effectiveness of neutrons and the effects of environmental low-dose irradiation.

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.

Relative biological effectiveness of neutrons: induction of malformations in a mouse strain with genetic predisposition.

Female hybrid mice (C57BL/6J x HLG) were exposed to 0.5 Gy of cyclotron neutrons (mean energy 5.8 MeV) after mating with HLG males when embryos were at the early zygote stage. Uterine contents were examined on gestation day 19 for prenatal mortality and malformed development. The results were compared to those obtained after irradiation of zygotes with 1.0 and 1.7 Gy X rays. The number of malformed fetuses was greater than for the unirradiated controls. Gastroschisis was the main observation, but exencephaly was also observed. The neutron relative biological effectiveness (RBE) for the induction of lethal events and malformations in the [(C57BL/6J x HLG)F(1)x HLG] mice was estimated. This value is higher than that for the RBE calculated for the HLG strain, which is known to be more sensitive to radiation than the hybrids.

Dose field in hiroshima and the risk of radiation-induced cancer

The dose distribution of γ-neutron radiation over the earth's surface as a result of the atomic explosion in Hiroshima is of decisive value for establishing the risk coefficients for death from radiation-induced cancer. At the same time, this radiation field is unique, since the ratio of its components varies both with distance from the hypocenter and with dose. For the DS 86 dosimetric system, the relation between mortality from solid cancer and dose has a linear, zero-threshold character. For this reason, the linear zero-threshold dependence is used as a basis for the entire system of radiation protection. However, the DS 86 results depend strongly on the choice of the coefficients of relative biological effectiveness of neutrons, which have not been established adequately. New data, which could change the dosimetric system and lead to a reexamination of the risk coefficients at low dose, are analyzed. 3 figures, 1 table, 7 references.

Relative biological effectiveness of neutrons for cancer induction and other late effects: a review of radiobiological data.

The risk of secondary cancer induction after a therapeutic irradiation with conventional photon beams is well recognised and documented. However, in general, it is totally overwhelmed by the benefit of the treatment. The same is true to a large extent for the combinations of radiation and drug therapy. After fast neutron therapy, the risk of secondary cancer induction is greater than after photon therapy. This can be expected from the whole set of radiobiological data, accumulated so far, which shows systematically a greater relative biological effectiveness (RBE) for neutrons for all the biological systems which have been investigated. Furthermore, the neutron RBE increases with decreasing dose and there is extensive evidence that neutron RBE is greater for cancer induction and for other late effects relevant in radiation protection than for cell killing at high doses as used in therapy. Almost no reliable human epidemiological data are available so far, and the aim of this work is to derive the best risks estimate for cancer induction after neutron irradiation and in particular fast neutron therapy. Animal data on RBE for tumour induction are analysed. In addition, other biological effects are reviewed, such as life shortening, malignant cell transformation in vitro, chromosome aberrations, genetic effects. These effects can be related, directly or indirectly, to cancer induction to the extent that they express a "genomic" lesion. Since neutron RBE depends on the energy spectrum, the radiation quality has to be carefully specified. Therefore, the microdosimetric spectra are reported each time they are available. Lastly, since heavy-ion beam therapy is being developed at several centres worldwide, the available data on RBE at low doses are reviewed. It can be concluded from this review that the risk of induction of a secondary cancer after fast neutron therapy should not be greater than 10-20 times the risk after photon beam therapy. For heavy ions, and in particular for carbon ions, the risk estimate should be divided by a factor of about 3 due to the reduced integral dose. The risk has to be balanced against the expected improvement in cure rate when the indication for high-LET therapy has been correctly evaluated in well-selected patient groups.

Neutron versus gamma-ray risk estimates. Inferences from the cancer incidence and mortality data in Hiroshima.

While it is recognized that neutrons contributed to the excess cancer incidence and mortality among the atomic bomb survivors in Hiroshima, there is no possibility to deduce the magnitude of this contribution from the data. This remains true even if the neutron doses in the dosimetry system DS86 are corrected upwards in line with recent neutron activation measurements. In spite of this fact, important information can be obtained in the form of an inverse relation of the risk coefficients for gamma-rays and neutrons. Such an interrelation must apply because the observed excess incidence or mortality is made up of a gamma-ray and a neutron component; increased attribution to neutrons decreases the attribution to photons. Computations with the uncorrected and the corrected DS86 are performed for the mortality and the incidence of solid tumors combined. They refer to doses up to 2 Gy and employ the constant relative risk model and a linear-quadratic dose dependence with variable ratio-the neutron relative biological effectiveness (RBE) at low doses-of the linear component for neutrons and gamma-rays. In line with past analyses, no quadratic component is obtained with the uncorrected DS86. but it is seen, even in these calculations, that the assumption of increased neutron RBEs does not translate into proportional increases of the risk coefficients of neutrons, because it leads to substantially reduced risk estimates for gamma-rays. Calculations with the corrected dosimetry bring out this reciprocity even more clearly. High values of the neutron RBE reduce-in line with recent suggestions by Rossi and Zaider-the risk estimates for gamma-rays substantially. Even a purely quadratic dose relation for gamma-rays is consistent with the data; it requires no major increase of the nominal risk coefficients for neutrons over the currently assumed values. The cancer data from Hiroshima can still provide 'prudent' risk estimates for photons, but with the corrected DS86, they do not prove that there is a linear component in the dose dependence for photons.

Neutron RBEs for cytopenia and repopulation of stroma and hematopoietic stem cells: mathematical models of marrow cell kinetics.

The objectives of this study were to (a) extend previous bone-marrow cell kinetics models that have been published for ionizing photons to include neutron radiations, and (b) provide Relative Biological Effectiveness (RBE) values for time-specific cell killing (cytopenia) and compensatory cellular proliferation (repopulation in response to toxic injury) for neutron doses ranging from 0.01 to 4.5 Gy delivered uniformly over one minute, hour, day, week, and month. RBEs for cytopenia of a cell lineage were based on ratios of protocol-specific doses that determined the same cell population nadir, whereas the RBEs for repopulation of a lineage were based on the ratios of protocol-specific doses that corresponded to the same total number of cells killed over the radiation treatments, and which should be replaced for long-term survival of the animal. Time-dependent RBEs were computed for neutron exposures relative to the effect of 60Co gamma rays given as a prompt dose. By the use of these RBE factors, low or variable dose rates, dose fractionations given over long periods of time, and different protocols involving several radiation qualities can be converted realistically, and by standard convention, into an equivalent dose of a reference radiation comprised of x or gamma rays given either as a pulse or at any other reference dose rate for which risk information based on epidemiological or animal dose-response data are available. For stromal tissues irradiated by fission neutrons, time-dependent RBEs for cytopenia were computed to range from 4.24 to 0.70 and RBEs for repopulation varied from a high of 6.88 to a low of 2.24. For hematopoietic stem cells irradiated by fission neutrons, time-dependent RBEs for cytopenia were computed to range from 5.02 to 0.22 and RBEs for repopulation varied from a high of 5.02 to a low of 1.98. RBEs based on tissue-kerma-free-in-air would be about twofold lower for isotropic cloud or rotational exposure geometries because marrow dose from isotropic neutron fields suffer factor-of-two greater attenuation than the gamma doses from gamma photons. For certain doses and dose rates, the RBE values computed for compensatory cellular proliferation clearly demonstrate the behavior that is commonly referred to as an inverse dose-rate effect, i.e., protraction of exposure may-under certain conditions-increase the magnitude of the dose response. Furthermore, because of non-linear rates for repair and repopulation, the highest RBEs are not necessarily found for the lowest doses nor the lowest RBEs always found at the highest doses.

Estimates of neutron relative biological effectiveness derived from the Japanese atomic bomb survivors

Purpose: To investigate neutron relative biological effectiveness. Materials and methods: The latest Japanese atomic bomb survivor cancer incidence and mortality datasets with the current (DS86) dosimetry system are analysed using generalized relative risk models and generalized absolute risk models, both with and without recently indicated adjustments to the Hiroshima DS86 neutron dose estimates. Results: Without adjustments to the Hiroshima neutron doses, the best estimate of neutron relative biological effectiveness for all tumours in the incidence data is 63.3 (95% CI 0-275.3) when a generalized relative risk model is used; when a generalized absolute risk model is used in the incidence data the best estimate is 53.5 (95% CI 0-201.0); when a generalized relative risk model is used in the mortality data, the best estimate is 287.7 (95% CI 38.0- 103). When likely adjustments are made to the Hiroshima neutron doses the best estimate of neutron relative biological effectiveness in the incidence data using a generalized relative risk model is 15.1 (95% CI 0-51.4); when a generalized absolute risk model is used in the incidence data the best estimate is 9.0 (95% CI 0-32.9); when a generalized relative risk model is used in the mortality data the best estimate is 55.1 (95% CI 9.5-280.3). Although there are no significant differences between groupings of the solid tumour sites in their estimated neutron relative biological effectiveness, there are indications that the neutron relative biological effectiveness of solid tumours is lower than that of leukaemia, whether or not adjustments are made to the Hiroshima neutron dose estimates. Uncertainties in the likely adjustments to the DS86 Hiroshima neutron and gamma dose estimates as well as uncertainties in the modelling of excess risk in the two cities (Hiroshima and Nagasaki) imply that these findings should be treated with caution. Conclusions: Likely adjustments to the Hiroshima neutron dose estimates imply a substantial increase in information on neutron relative biological effectiveness. Whether or not adjustments are made to the Hiroshima neutron doses, there are indications of inconsistency between the estimates of neutron relative biological effectiveness for solid tumours and leukaemia. Dosimetric and modelling uncertainties mean that these findings should be treated with caution.

The risk of non-melanoma skin cancer incidence in the Japanese atomic bomb survivors

The latest Japanese atomic bomb survivor nonmelanoma skin cancer incidence dataset is analysed and indicates substantial curvilinearity in the dose-response curve, consistent with a possible dose threshold of about 1 Sv, or with a doseresponse in which the excess relative risk is proportional to the fourth power of dose, with a turning-over in the dose-response at high doses (3 Sv). The time distribution of the radiationinduced excess risk is best described by a model in which the relative excess risk is proportional to a product of powers of time since exposure and attained age. The fits of generalized relative risk models with exponential functions of time and age at exposure (and in particular of attained age) to adjust the relative risk are less satisfactory, as also are the fits of other models in which products of powers of time since exposure, age at exposure and attained age adjust the excess absolute risk. Sensitivity analyses indicate the importance of likely adjustments to the Hiroshima neutron doses for the optimal model parameters, particularly if values of the neutron relative biological effectiveness (RBE) of more than 5 are assumed. If adjustments recently proposed are made to the Hiroshima neutron doses, then using the optimal model (in which excess risk is proportional to the fourth power of dose) the best estimate of the neutron RBE is 1.3 (95%CI 07.1). However, uncertainties in skin dose estimates for the atomic bomb survivors means that the findings with respect to the neutron RBE and the non-linearity in the dose-response curve should be treated with caution.

Distinct difference in relative biological effectiveness of 252Cf neutrons for the induction of mitotic crossing over and intragenic reversion of the white-ivory allele in Drosophila melanogaster

The relative biological effectiveness (RBE) of 252Cf neutrons was determined for two different types of somatic mutations, i.e., loss of heterozygosity for wing-hair mutations and reversion of the mutant white-ivory eye-color, in Drosophila melanogaster. Loss of heterozygosity for wing-hair mutations results predominantly from mitotic crossing over induced in wing anlage cells of larvae, while the reverse mutation of eye-color is due to an intragenic structural change in the white locus on the X-chromosome. For a quantitative comparison of RBE values for these events, we have constructed a combined mutation assay system so that induced mutant wing-hair clones as well as revertant eye-color clones can be detected simultaneously in the same individuals. Larvae were irradiated at the age of 80 ± 4 h post-oviposition with 252Cf neutrons or 137Cs γ-rays, and male adult flies were examined under the microscope for the presence of the two types of clonal mosaic spots appearing. The induction of wing-hair spots per dose unit was much greater for 252Cf neutrons than for 137Cs γ-rays, whereas the frequencies of eye-color reversion were similar for neutrons and γ-rays. The estimated RBE values of neutrons were 8.5 and 1.2 for the induction of mutant wing-hair spots and revertant eye-color spots, respectively. These results indicate that the RBE of neutrons is much greater for mitotic crossing over in comparison to the intragenic white-ivory reversion events. Possible causes for the difference in RBE are discussed.