Cytogenetic effects induced in vitro in human peripheral blood lymphocytes by neutrons. II. Relative biological effectiveness of neutrons having different energies]

Human lymphocytes were irradiated in vitro during Go stage by graded doses of thermal neutrons and neutrons having an average energy of 0.04; 0.09; 0.35; 0.85 and 14,7 MeV as well as by 60Co gamma rays, and RBE of neutrons relative to gamma-rays was calculated for the frequency of total and different types of aberrations. It was found that the RBE has the most value at the low doses and decreases when the exposition dose increases. 0.35 MeV neutrons have the maximum RBE in comparison with neutrons having other energies. When comparing the RBE values calculated for different types of chromosome aberrations, it was found out that dicentrics and dicentrics plus centric rings had more RBE than acentric aberrations (pair fragments and minutes).     

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.     

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 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.     

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

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

Renal damage in the mouse: the effect of d(4)-Be neutrons

A further study on the response of the mouse kidney to d(4)-Be neutrons (EN = 2.3 MeV) is described. The results confirm and augment the work published previously by Stewart et al. [Br. J. Radiol. 57, 1009-1021 (1984)]; the present paper includes the data from a "top-up" design of experiment which extends the measurements of neutron RBE (relative to 240 kVp X rays) down to X-ray doses of 0.75 Gy per fraction. The mean RBE for these neutrons increases from 5.8 to 7.3 as X-ray dose per fraction decreases from 3.0 to 1.5 Gy in the kidney. This agrees with the predictions from the linear quadratic (LQ) model, based on the renal response to X-ray doses above 4 Gy per fraction. The mean RBE estimate from a single dose group at 0.75 Gy per fraction of X rays is, however, 3.9. This is below the LQ prediction and may indicate increasing X-ray sensitivity at low doses. Data from this study and from those published previously have been used to determine more accurately the shape of the underlying response to d(4)-Be neutrons; an alpha/beta ratio of 20.5 +/- 3.7 Gy was found. The best value of alpha/beta for X rays determined from these experiments was 3.04 +/- 0.35 Gy, in agreement with previous values.     

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.     

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.     

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.     

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.     

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.     

The production of chromosome aberration in Chinese hamster fibroblasts exposed to 24 keV neutrons

A filtered reactor beam, consisting mainly of 24 keV neutrons, was used to study the induction of chromosome aberrations in the V79/4(AH1) Chinese hamster cell line. The yields of both dicentrics and acentrics were linear with dose and the value of relative biological effectiveness (RBE) for dicentrics at low doses was 6.5 +/- 1.4. This value was similar to that found previously for a neutron spectrum with mean energy 2.1 MeV, and suggests that the RBE of neutrons does not increase to very high values in the energy region below 100 keV. This result does not support the suggestions of Davy (1969) and Key (1971) that the neutron RBE rises to very high values in the intermediate energy range.     

Tumor induction and life shortening in BC3F1 female mice at low doses of fast neutrons and X rays

Extension of previous investigations at this laboratory regarding life shortening and tumor induction in the mouse has provided more complete dose-response information in the low dose region of X rays and neutrons. A complete observation of survival and late pathology has been carried out on over 2000 BC3F1 female mice irradiated with single doses of 1.5 MeV neutrons (0.5, 1, 2, 4, 8, 16 cGy) and, for comparison, of X rays (4, 8, 16, 32, 64, 128, 256 cGy). Data analysis has shown that a significant life shortening is observable only for individual neutron doses not lower than 8 cGy. Nevertheless, assuming a linear nonthreshold form for the overall dose-effect relationships of both radiation qualities, an RBE value of 12.3 is obtained for the 1.5 MeV neutrons. The induction of solid tumors by neutrons becomes statistically significant at individual doses from 8 cGy and by X rays for doses larger than 1 Gy. Linear dependence on neutron dose appears adequate to interpret the data at low doses. A separate analysis of ovarian tumor induction substantiates the hypothesis of a threshold dose for the X rays, while this is not strictly needed to interpret the neutron data. A trend analysis conducted on the neoplasm incidence confirms the above findings. Death rates have been analyzed, and a general agreement between the shift to earlier times of these curves and tumor induction was found.     

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).     

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.     

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.     

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.     

The relative biological effectiveness of 10B-neutron capture therapy for early skin reaction in the hamster

The relative biological effectiveness (RBE) of 10B-neutron capture therapy (BNCT) on skin was analyzed using hamsters. The Kyoto University Research Reactor, which has a very low contamination of gamma rays and fast neutrons, was used as a thermal neutron source. Boron-10-para-boronophenylalanine hydrochloride ([10B]BPA.HCl) was administered to the hamsters. The evolution and time course of early skin reactions were assessed. These reactions were compared with those produced by electron beams. The maximum safe skin doses (no more than moist desquamation) of BNCT and electron beams were established to be 11 and 21 Gy, respectively. The RBE at this single dose with BNCT was found to be 1.94, assuming that the RBE of the gamma rays was 1.0 and each component of BNCT (mixed radiations) was simply additive.     

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.     

Comparison of recovery from potential mitotic abnormality in mitotically quiescent lens cells after X, neutron, and 56Fe irradiations

After exposure to various doses of 250 kVp X radiation, 0.85 Me V fission spectrum neutrons, or 600 MeV/A iron (Fe) particles, mitotically quiescent rat lens cells showed no visible evidence of radiation injury. However, following the mitogenic stimulus of wounding, mitotic abnormalities became evident when responding cells entered mitosis. Latent damage and recovery therefrom were monitored at 3, 7, 14, and 28 days after irradiation. Following doses of 1 to 10 Gy of X radiation, the recovery rate, indicated by a decrease in abnormalities with time, was proportional to dose, and the dose-effect slope decreased exponentially with time. Virtually no recovery occurred during the 28 days after 1.25 to 2.25 Gy of fission neutron radiation. After doses of 0.5 to 3.0 Gy of Fe particles, an increased expression of mitotic damage or recovery than recovery occurred. As a consequence of the differing patterns in time for expression of damage or recovery following X rays and the high-LET radiations, the relative biological effectiveness (RBE) increased from 3.6 to 16 for neutrons and from 2 to 10 for Fe particles over the 28-day observation period.