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Analysis of secondary electron emission spectra of equal-LET protons and alpha particles for purposes of radiation quality and spaceflight hazard assessment.

Amongst the great variety of heavy particles present in the galactic and solar cosmic ray spectra, hydrogen and helium nuclei are significantly more abundant than all other heavier ions and, as such, represent a major radiation hazard to humans in space. Experimental data have suggested that differences in relative biological effectiveness (RBE) exist between the two species at the same value of linear energy transfer (LET). This has consequences for heavily ionising radiation protection procedures, which currently still assume a simple dependence of radiation quality on LET. By analysing the secondary electron (delta-ray) emission spectra of protons and alpha particles, in terms of the spatial characteristics of energy deposition in cellular targets and the likelihood of complex lesion formation, a numerical quantity representing biological effectiveness is generated. When expressed relative to a reference radiation, this quantity is found to differ for protons and a particles of the same LET, demonstrating not only the ion-specific nature of RBE but also the inadequacy of specifying radiation quality as a function of LET only. Such a method for numerically assessing radiation quality may have implications for procedures for heavy ion protection in space at low doses and for understanding the initial mechanisms of radiation action.

Alpha Particles↗

Controllable passive detectors for study of the radiation environment in space and the atmosphere.

We propose to study the radiation environment on board different flight vehicles: cosmos-type satellites, orbital stations, Space Shuttles and civil (sonic and supersonic) aircraft. These investigations will be carried out with single type of passive detector, namely, nuclear photoemulsions (NPE) with adjustable threshold of particle detection within broad range of linear energy transfer (LET) that is done by means of the technique of selective development of NPE exposed in space. These investigations will allow, one to determine: integral spectra of LET of charged particles of cosmic ray (CR) over a wide range from 2.0 to 5 x 10(4) MeV/cm in biological tissue; differential energy spectra of fast neutrons (1-20 MeV); estimation of absorbed and equivalent doses from charged and neutral component CR; charge and energy spectra of low energy nuclei (E < or = 100 MeV) with Z > or = 2 having in view the extreme hazard radiation to biological objects and microelectronic schemes taken on board inside and outside of these different flight vehicles with exposures from several days to several months. The investigation of radiation environment on board the airplanes depending on the flight parameters will be conducted using emulsions of different sensitivity without any controlling of threshold sensitivity (Akopova et al., 1996). The proposed detector can be used in the joint experiments on the new International Cosmic Station "Alpha".

Aircraft↗

Microdosimetric characteristics of the clinical proton beams at JINR, Dubna.

High-energy proton radiotherapy beams give rise to secondary heavy charged particles with elevated linear energy transfer (LET), which contribute to the dose in a patient. This contribution to the characteristics of radiotherapy proton beams was experimentally studied by means of a LET spectrometer based on a track detector. The spectrometer permits LET spectra to be established in the region above 10 keV.micron-1 in tissue. Sets of track detectors were exposed in the various depths of a phantom irradiated with protons of two energies, 150 and 205 MeV. It was observed that the contribution of particles with the values of LET mentioned increases with the depth, representing from about 2 (at the surface) up to few tens% close to Bragg peak region of the total dose. There, some of primary protons contribute also above 10 keV.micron-1. Using the 'biological weighted function' proposed, the clinical RBE was calculated, it could approach 1.3. This effect has to be taken into account during the clinical beam production and the radiotherapy.

Linear Energy Transfer↗

Relative biological effectiveness for cell-killing effect on various human cell lines irradiated with heavy-ion medical accelerator in Chiba (HIMAC) carbon-ion beams.

PURPOSE: To clarify the relative biological effectiveness (RBE) values of various human cell lines for carbon-ion beams with 2 different linear energy transfer (LET) beams and to investigate the relationship between the cell-killing effect and the biophysical characters, such as the chromosome number and the area of the cell nucleus, using qualitatively different kinds of radiations. METHODS AND MATERIALS: Sixteen different human cell lines were irradiated with carbon-ion beams, having 2 different LET values (LET(infinity) = 13.3 and approximately 77 keV/microm), accelerated by the Heavy Ion Medical Accelerator in Chiba (HIMAC) at National Institute of Radiological Sciences in Japan. Cell-killing effect was detected as reproductive cell death using a colony-formation assay. The number of chromosomes was observed in a metaphase spread using the conventional method. The area of the cell nucleus was calculated as an ellipse on photographs using a micrometer. RESULTS: The RBE values calculated by the D(10), which is determined as the dose (Gy) required to reduce the surviving fraction to 10%, relative to X-rays, range from 1.06 to 1.33 for 13-keV/microm-beam and from 2.00 to 3. 01 for approximate 77-keV/microm-beam irradiation on each cell line. There was a good correlation in the D(10) values of each cell line between X-rays and carbon-ion beams. However, the D(10) values did not clearly depend on either the chromosome number or the area of the cell nuclei. CONCLUSION: The RBE values for HIMAC carbon-ion beams are consistent with previous reports using carbon-ion beams with the similar LET values, and the cellular radiosensitivity of different cell lines well correlate among different types of radiation.

Brain Neoplasms↗

Low and high LET radiation-induced apoptosis in M059J and M059K cells.

PURPOSE: To investigate and compare the ability of DNA-dependent protein kinase (DNA-PK)-deficient and -proficient cells to undergo apoptosis after exposure to low and high linear energy transfer (LET) radiation. MATERIALS AND METHODS: A human glioma cell line M059J lacking the catalytic subunit of DNA-PK (DNA-PKcs) and its DNA-PKcs-proficient counterpart, M059K, were exposed to 1 and 4 Gy of accelerated nitrogen ions (14N, 140 eV nm(-1), 8-12 Gy min(-1)) or 60Co gamma-rays (0.2 eV nm(-1), 0.7 Gy min(-1)). The induction of apoptosis was studied up to 144 h post-irradiation using two different methods: morphological characterization of apoptotic cells after fluorescent staining and cell size distribution analysis to detect apoptotic bodies. In parallel, protein expression of DNA-PKcs and poly(ADP-ribose) polymerase (PARP) as well as DNA-PK and caspase-3 activity were investigated. RESULTS: Low and high LET radiations (4 Gy) induced a time-dependent apoptotic response in both cell lines. Low LET radiation induced a significantly elevated apoptotic response in M059J as compared with M059K cells at 144 h post-irradiation. Following high LET radiation exposure, there was no difference between the cell lines at this time. PARP cleavage was detected in M059J cells following both low and high LET irradiation, while only high LET radiation induced PARP cleavage in M059K cells. These cleavages occurred in the absence of caspase-3 activation. CONCLUSIONS: M059J and M059K cells both display radiation-induced apoptosis, which occur independently of caspase-3 activation. The apoptotic course differs between the two cell lines and is dependent on the quality of radiation.

Apoptosis↗

Carbon beam therapy overcomes the radiation resistance of uterine cervical cancer originating from hypoxia.

PURPOSE: High linear energy transfer (LET) particles are believed to decrease tumor radiation resistance originating from hypoxia. However, no proof of this effect has been provided by clinical trials and related clinical research. Hence, we investigated the radiation biological aspects of high LET carbon beam therapy on cervical cancer. EXPERIMENTAL DESIGN: This study involved 49 patients with stage IIIb bulky and stage IVa cervical cancer treated with high LET carbon beams between October 1995 and June 2000. Oxygen partial pressure (pO(2)) was measured by using a needle-type polarographic oxygen electrode. RESULTS: The 4-year disease-free survival rates of patients with pO(2) </= 20 mm Hg (hypoxic tumor) and pO(2) > 20 mm Hg (oxygenated tumor) before treatment were 37% and 21%, respectively. The local control rates of hypoxic and oxygenated tumors before treatment were 58% and 54%, respectively. The disease-free survival rates of hypoxic and oxygenated tumors assessed by oxygen status at the 5th day of irradiation were 33% and 32%, respectively. The local control rates of hypoxic and oxygenated tumors at the 5th day were 60% and 58%, respectively. There was no significant prognostic difference between hypoxic and oxygenated tumors. CONCLUSION: The similar disease-free survival and local control rates between hypoxic and oxygenated tumors before and during treatment indicated that the role of the tumor oxygenation status was not so important in local control in carbon beam therapy. These results indicated that high LET carbon beam irradiation might reduce the radiation-resistant nature stemming from tumor hypoxia.

Carbon↗

DNA lesion complexity and induction of apoptosis by ionizing radiation.

PURPOSE: To determine whether murine lymphoid cell lines can discriminate between high- and low-LET (linear energy transfer) radiation-induced DNA lesions. MATERIALS AND METHODS: Sensitivity to killing by DNA-incorporated 3H and 125I decays, accumulated during storage in the gas phase of a liquid nitrogen tank, was determined by clonogenic survival assay. RESULTS: Induction of a lethal event in the STRij-4-2.2, WEHI-22.1, and L5178Y-R cell lines required approximately 30 times more 3H than 125I decays. Hence, the same ratio of 3H to 125I decays was found irrespective of whether the cell lines contained mutant or wild-type p53 and irrespective of whether they underwent rapid interphase or mitosis-related apoptosis after irradiation. The 18-81 cell line differed in showing a ratio of around 21 and it is argued that this may be a consequence of v-ABL over-expression. The assumption that DNA-incorporated 3H and 125I decays are low- and high-LET-like events respectively was confirmed by the similar sensitivity of L5178Y-R and -S cells to killing by 125I decays in contrast with their difference in sensitivity to 3H decays. CONCLUSIONS: The difference in lethal effectiveness between DNA-incorporated 3H and 125I decays can be explained by the hypothesis that simple DSB (double-strand breaks) are non-lethal and that cell killing is attributable to complex DSB. The low-LET radiation-specific sensitization of L5178Y-S cells may reflect defective repair of a DNA lesion class (presumably simple DSB) that is differentially induced by high- and low-LET radiation and is non-lethal to cells with normal repair capacity.

Animals↗

Biological effectiveness of isolated short electron tracks: V79-4 cell inactivation following low dose-rate irradiation with Al(K) ultrasoft X-rays.

PURPOSE: To investigate the biological effect of single, isolated, short electron tracks (<70 nm) relevant to practical human exposures to low-linear energy transfer radiation. MATERIALS AND METHODS: An irradiation rig was constructed that allowed environmentally controlled, protracted irradiations with an individually prescribed dose to up to 20 samples over a period of days. Inactivation of V79-4 mammalian cells by Al(K) ultrasoft X-rays was studied at high and low dose-rates with a maximum exposure time of 42 h. RESULTS: A significant increase in clonogenic survival was observed at the higher doses when the exposure time was increased from <6 min to 21 h, with no further increase observed for 42-h exposures. Despite the short range of the low-energy electrons produced (<70 nm), significant cell inactivation was observed for these low dose-rate exposures. CONCLUSIONS: The results are consistent with the hypothesis that even individual tracks can be biologically effective.

Aluminum↗

Estimation of radiation tolerance to high LET heavy ions in an anhydrobiotic insect, Polypedilum vanderplanki.

PURPOSE: Anhydrobiotic larvae of Polypedilum vanderplanki are known to show an extremely high tolerance against a range of stresses. We have recently reported that this insect withstands exposure to high doses of gamma-rays (linear energy transfer [LET] 0.2 keV/microm). However, its tolerance against high LET radiation remains unknown. The aim of this study is to characterize the tolerance to high-LET radiations of P. vanderplanki. MATERIALS AND METHODS: Larval survival and subsequent metamorphoses were compared between anhydrobiotic (dry) and non-anhydrobiotic (wet) samples after exposure to 1 - 7000 Gy of three types of heavy ions delivered from the azimuthally varying field (AVF) cyclotron with LET values ranging from 16.2 - 321 keV/microm. The tolerance against 4He ions was also compared among three chironomid species. RESULTS: At all LET values measured, dry larvae consistently showed greater radiation tolerance than hydrated larvae, perhaps due to the presence of high concentrations of the disaccharide trehalose in anhydrobiotic animals, and the radiation-induced damage became evident at lower doses as development progressed. Relative biological effectiveness (RBE) values based on the median inhibitory doses reached a maximum at 116 keV/microm (12C), and the maximum RBE clearly increased as development progressed. Lower D0 (dose to reduce survival from relative value 1.00 - 0.37 on the exponential part of the survival curve), and higher Dq (quasi-threshold dose) were found in individuals exposed to 4He ions, compared to gamma-rays, and in P. vanderplanki larvae compared to non-anhydrobiotic chironomids. CONCLUSION: Anhydrobiosis potentiates radiation tolerance in terms of larval survival, pupation and adult emergence of P. vanderplanki exposed to high-LET radiations as well as to low-LET radiation. P. vanderplanki larvae might have more efficient DNA damage repair after radiation than other chironomid species.

Animals↗

Reoxygenation of human coronary smooth muscle cells suppresses HIF-1alpha gene expression and augments radiation-induced growth delay and apoptosis.

BACKGROUND AND PURPOSE: Catheter-based coronary brachytherapy with beta- and gamma-radiation is an evidence-based method to prevent restenosis after percutaneous transluminal coronary angioplasty (PTCA) and stent implantation, but the outcome may be subject to improvements. Physiological studies suggest that most of the target cells of brachytherapy in coronary arteries after PTCA are hypoxic. A lack of oxygen decreases the effect of low LET (linear energy transfer) irradiation. The authors assumed that reoxygenation of hypoxic human coronary smooth muscle cells (HCSMCs) improves the results of coronary brachytherapy. The expression of hypoxia-inducible factor 1alpha (HIF-1alpha) gene, and the rates of growth and apoptosis of hypoxic and reoxygenated HCSMCs after gamma-irradiation were therefore analyzed. MATERIAL AND METHODS: An in vitro model of megacolonies of HCSMCs was developed. After exposure to chronic hypoxia the HCSMCs were irradiated with graded doses of 2, 4, 8, and 16 Gy using a (60)Co source either under hypoxia (pO(2) < 3 mmHg) or after reoxygenation (pO(2) approximately 150 mmHg). RT-PCR (reverse transcription-polymerase chain reaction) analysis was used to quantify HIF-1alpha gene expression and the growth of HCSMC megacolonies was measured serially. The oxygen enhancement ratio (OER) was calculated from the specific growth delay. Apoptosis of HCSMCs was quantified by counting cells with specific DNA strand breaks using the TUNEL assay. RESULTS: HIF-1alpha gene expression was markedly suppressed in reoxygenated cells versus hypoxic cells 30 min after gamma-irradiation at all radiation doses (158 +/- 46% vs. 1,675 +/- 1,211%; p < 0.01). Apoptosis was markedly increased in reoxygenated HCSMCs. The OER was 1.8 (95% CI [confidence interval] 1.3-2.4). Therefore, reoxygenated HCSMCs require 44% less radiation dose to achieve the equivalent biological radiation effect compared to hypoxic HCSMCs. CONCLUSION: Reoxygenation of coronary smooth muscle cells should be considered an option to increase efficacy of coronary brachytherapy. This could be used to reduce radiation dose and associated late side effects.

Angioplasty, Balloon, Coronary↗

Issues in risk assessment from solar particle events.

Uncertainties in risk assessment from solar particle events (SPE) include the role of high linear energy transfer (LET) secondary ions, the assessment of dose-rate effects as they relate to acute injury, the risk of cancer mortality and the modification of health effects due to the stress of spaceflight. We discuss several issues where new knowledge is required for improving estimates of radiation risk from SPE's. Secondary particles such as neutrons and low energy and charge ions (LZE) may dominate radiation risk behind a storm shelter and their biological effects are poorly understood, especially at low dose-rate. Dose-rate modulation of radiation response is also related to genetic pre-disposition an important determinant of radiation sensitivity. Molecular pathways that control cell death and tissue response have been elucidated in recent years and should provide new understanding of dose-rate effects for risk assessment. We consider some of these factors and discuss calculations using radiation transport codes, track structure models of energy deposition, and a molecular kinetics approach to model radiation response.

Apoptosis↗

Analysis of MIR-18 results for physical and biological dosimetry: radiation shielding effectiveness in LEO.

We compare models of radiation transport and biological response to physical and biological dosimetry results from astronauts on the Mir space station. Transport models are shown to be in good agreement with physical measurements and indicate that the ratio of equivalent dose from the Galactic Cosmic Rays (GCR) to protons is about 3/2:1 and that this ratio will increase for exposures to internal organs. Two biological response models are used to compare to the Mir biodosimetry for chromosome aberration in lymphocyte cells; a track-structure model and the linear-quadratic model with linear energy transfer (LET) dependent weighting coefficients. These models are fit to in vitro data for aberration formation in human lymphocytes by photons and charged particles. Both models are found to be in reasonable agreement with data for aberrations in lymphocytes of Mir crew members: however there are differences between the use of LET dependent weighting factors and track structure models for assigning radiation quality factors. The major difference in the models is the increased effectiveness predicted by the track model for low charge and energy ions with LET near 10 keV/micrometers. The results of our calculations indicate that aluminum shielding, although providing important mitigation of the effects of trapped radiation, provides no protective effect from the galactic cosmic rays (GCR) in low-earth orbit (LEO) using either equivalent dose or the number of chromosome aberrations as a measure until about 100 g/cm 2 of material is used.

Chromosome Aberrations↗

Microdosimetry spectra of the Loma Linda proton beam and relative biological effectiveness comparisons.

Protons have long been recognized as low LET radiation in radiotherapy. However, a detailed account of LET (linear energy transfer) and RBE (relative biological effectiveness) changes with incident beam energy and depth in tissue is still unresolved. This issue is particularly important for treatment planning, where the physical dose prescription is calculated from a RBE using cobalt as the reference radiation. Any significant RBE changes with energy or depth will be important to incorporate in treatment planning. In this paper we present microdosimetry spectra for the proton beam at various energies and depths and compare the results to cell survival studies performed at Loma Linda. An empirically determined biological weighting function that depends on lineal energy is used to correlate the microdosimetry spectra with cell survival data. We conclude that the variations in measured RBE with beam energy and depth are small until the distal edge of the beam is reached. On the distal edge, protons achieve stopping powers as high as 100 keV/micron, which is reflected in the lineal energy spectra taken there. Lineal energy spectra 5 cm beyond the distal edge of the Bragg peak also show a high LET component but at a dose rate 600 times smaller than observed inside the proton field.

Animals↗

Effects of single-pulse (< or = 1 ps) X-rays from laser-produced plasmas on mammalian cells.

The effects of low linear energy transfer (LET) radiation on mammalian cells have been studied at dose-rates as high as 10(9) Gy/sec delivered as a single 3-nanosecond pulse, and no increase in cytotoxicity was shown compared with delivery at a conventional dose-rate. There have been no observations on the effects of radiation delivered at even higher dose-rates on the picosecond time-scale. Here we examined, for the first time, the effects on cultured mouse L5178Y cells and its radiosensitive XRCC4-deficient mutant M10 cells of sub-picosecond X-rays emitted from laser-produced plasmas at the ultrahigh dose-rate of 10(12)-10(13) Gy/sec. No increase in the sensitivity to the X-rays was observed compared with gamma-rays at a conventional dose-rate. The increase in the sensitivity of L5178Y cells by labeling with 5-iododeoxyuridine was smaller than those irradiated with gamma-rays at a conventional dose-rate, while the difference was apparently the reverse in M10 cells. The D10 ratio between L5178Y cells and M10 cells produced by the X-rays at temporally dense ionization was the same as that produced by X(gamma)-rays at the conventional dose-rate, while the ratio is greatly reduced in the case of particle radiation. These results suggest that there is no increase in the cytotoxic effects of X-rays at dose-rates as high as 10(13) Gy/sec, and that the increased cytotoxicity of particle radiation is not attributable to temporally dense ionization. It is discussed that the mechanism for the induction of radiation damage responsible for cytotoxicity may be slightly modified at ultrahigh dose-rates.

Animals↗

An assessment of galactic cosmic radiation quality considering heavy ion track structures within the cellular environment.

Beyond the magnetic influence of the Earth, the flux of galactic cosmic radiation (GCR) represents a radiological concern for long-term manned space missions. Current concepts of radiation quality and equivalent dose are inadequate for accurately specifying the relative biological "efficiency" of low doses of such heavily ionising radiations, based as they are on the single parameter of Linear Energy Transfer (LET). Such methods take no account of the mechanisms, nor of the highly inhomogeneous spatial structure, of energy deposition in radiation tracks. DNA damage in the cell nucleus, which ultimately leads to the death or transformation of the cell, is usually initiated by electrons liberated from surrounding molecules by the incident projectile ion. The characteristics of these emitted "delta-rays", dependent primarily upon the charge and velocity of the ion, are considered in relation to an idealised representation of the cellular environment. Theoretically calculated delta-ray energy spectra are multiplied by a series of weighting algorithms designed to represent the potential for DNA insult in this environment, both in terms of the quantity and quality of damage. By evaluating the resulting curves, and taking into account the energy spectra of heavy ions in space, a relative measure of the biological relevance of the most abundant GCR species is obtained, behind several shielding configurations. It is hoped that this method of assessing the radiation quality of galactic cosmic rays will be of value when considering the safety of long-term manned space missions.

Algorithms↗

Dose and time dependent apoptotic response in a human melanoma cell line exposed to accelerated boron ions at four different LET.

The aim was to investigate and compare the influence of linear energy transfer (LET), dose and time on the induction of apoptosis in a human melanoma cell line exposed to accelerated light boron ((10)B) ions and photons. Cells were exposed in vitro to doses up to 6 Gy accelerated boron ions (40, 80, 125 and 160 eV nm(-1)) and up to 12 Gy photons (0.2 eV nm(-1)). The induction of apoptosis was measured up to 9 days after irradiation using morphological characterization of apoptotic cells and bodies. In parallel, measurements of cell-cycle distribution, monitored by DNA flow cytometry, and cell survival based on the clonogenic cell survival assay, were performed. In addition, the induction and repair of DNA double-strand breaks (DSB), using pulsed-field gel electrophoresis (PFGE) were studied. Accelerated boron ions induced a significant increase in apoptosis as compared with photons at all time points studied. At 1-5 h the percentage of radiation-induced apoptotic cells increased with both dose and LET. At the later time points (24-216 h) the apoptotic response was more complex and did not increase in a strictly LET-dependent manner. The early premitotic apoptotic cells disappeared at 24 h following exposure to the highest LET (160 eV nm(-1)). A postmitotic apoptotic response was seen after release of the dose-, time- and LET-dependent G2/M accumulations. The loss of clonogenic ability was dose- and LET-dependent and the fraction of un-rejoined DSB increased with increasing LET. Despite the LET-dependent clonogenic cell killing, it was not possible to measure quantitatively a LET-dependent apoptotic response. This was due to the different time course of appearance and disappearance of apoptotic cells.

Apoptosis↗

Induction of homologous recombination in the hprt gene of V79 Chinese hamster cells in response to low- and high-LET irradiation.

Dense ionization tracks from high linear energy transfer (LET) radiations form multiple damaged sites (MDS), which involve several types of DNA lesions in close vicinity. The primary DNA damage triggers sensor proteins that activate repair processes, cell cycle control or eventually apoptosis in subsequent cellular responses. The question how homologous recombination (HR) and non-homologous end joining (NHEJ) interact in the repair of radiation-induced DNA damage of MDS type has been addressed in different model systems but several questions remain to be answered. We have therefore challenged cells with treatments of ionizing radiation of different qualities to investigate whether primary DNA damages of different complexity are reflected in the processes of repair by HR as well as cell survival. We used the V79 derived SPD8 cell line to determine the induction of HR in the hprt exon 7 and clonogenic assay for survival in response to radiation. SPD8 cells were irradiated with gamma-rays (137Cs 0.5 keV/microm), boron ions (40 and 80 keV/microm) and nitrogen ions (140 keV/microm), with doses up to 5 Gy. Analysis of clonogenic survival showed that B-ions (80 keV/microm) and N-ions were more toxic than gamma-rays, 4.1 and 5.0 times respectively, while B-ions at 40 keV/microm were 2.0 times as toxic as gamma-rays. Homologous recombination in the cells exposed to B-ions (80 keV/microm) increased 2.9 times, a significant response as compared to cells exposed to gamma-rays, while for B-ions (40 keV/microm) and N-ions a nonsignificant increase in HR of 1.2 and 1.4, respectively, was observed. We hypothesize that the high-LET generated formation of MDS is responsible for the enhanced cytotoxicity as well as for the mobilization of the HR machinery.

Animals↗

Radiation quality and risk estimation in relation to space missions.

While Q is specified as a function of linear energy transfer (LET) in practice the Q for neutrons has been selected by a judgment decision based on the relative biological effectiveness (RBE) to induce stochastic effects. There are no RBE values for tumor induction by heavy ions or protons in humans. Thus, selection of Q values has been based either on LET (or lineal energy) or RBEs from animal experiments. Estimates of Q for heavy ions in low earth orbit (LEO) range from about 5 to 14. The average Q value of all radiation in LEO has been estimated to be about 1.3. There is a lack of experimental data for RBEs for heavy ions but RBE increases as a function of LET. In the case of the Harderian gland the RBE reaches a maximum of 25-30 between about 100-200 keV/micrometer but does not appear to decrease at higher LETs. The International Commission of Radiological Protection have proposed the use of radiation weighting factors in lieu of quality factors. The weighting factors will range from 1 to 20.

Animals↗