Low Dose-rate Exposure Research Articles

Usefulness and limits of biological dosimetry based on cytogenetic methods

Damage from occupational or accidental exposure to ionising radiation is often assessed by monitoring chromosome aberrations in peripheral blood lymphocytes, and these procedures have, in several cases, assisted physicians in the management of irradiated persons. Thereby, circulating lymphocytes, which are in the G0 stage of the cell cycle are stimulated with a mitogenic agent, usually phytohaemagglutinin, to replicate in vitro their DNA and enter cell division, and are then observed for abnormalities. Comparison with dose-response relationships obtained in vitro allows an estimate of exposure based on scoring: Unstable aberrations by the conventional, well-established analysis of metaphases for chromosome abnormalities or for micronuclei; So-called stable aberrations by the classical G-banding (Giemsa-Stain-banding) technique or by the more recently developed fluorescent in situ hybridisation (FISH) method using fluorescent-labelled probes for centromeres and chromosomes. Three factors need to be considered in applying such biological dosimetry: (1) Radiation doses in the body are often inhomogeneous. A comparison of the distribution of the observed aberrations among cells with that expected from a normal poisson distribution can allow conclusions to be made with regard to the inhomogeneity of exposure by means of the so-called contaminated poisson distribution method; however, its application requires a sufficiently large number of aberrations, i.e. an exposure to a rather large dose at a high dose rate. (2) Exposure can occur at a low dose rate (e.g. from spread or lost radioactive sources) rendering a comparison with in vitro exposure hazardous. Dose-effect relationships of most aberrations that were scored, such as translocations, follow a square law. Repair intervening during exposure reduces the quadratic component with decreasing dose rate as exposure is spread over a longer period of time. No valid solution for this problem has yet been developed, although, in theory, both deterministic damage and aberrations might be repaired to a similar degree; a comparison of aberrations following a linear dose relationship might also help when the doses have been sufficiently large. (3) Investigations might have been possible only a certain time after the exposure. The relatively rapid disappearance of lymphocytes carrying unstable aberrations limits their use in retrospective dosimetry, years after exposure. Scoring stable aberrations, thought to persist in the circulating lymphocytes, might appear more appropriate in such situations. However, the examination of a representative number of cells by G-banding is extremely laborious, and the FISH method is not only expensive but has not yet been fully validated in different laboratories. In conclusion, biological dosimetry has serious limitations exactly for situations where the need for information is most urgent. It renders its most useful results when an individual has been exposed to a rather homogeneous high-level radiation over a short time interval, i.e. accidents at high-intensity radiation devices. On the other hand, it yielded less satisfactory information even when the most recent techniques were used for situations, where a low level, low dose rate exposure has occurred at some time in the past, for example for persons living in areas contaminated from the Chernobyl accident. Such negative experiences should be kept in mind in order to avoid futile and expensive investigations in the case of populations exposed from radioactivity and, notably, also from potentially clastogenic chemical agents.

Commentary on information that can be drawn from studies of areas with high levels of natural radiation

Studies of the health of populations living in areas of high levels (HL) of natural radiation are a potentially important source of information on the effects of chronic low-dose rate exposures to ionising radiation. The current paper presents a brief overview of the status of studies in Brazil, China, India, and Iran. At present, only limited information on health risks can be drawn. Issues of concern in the interpretation of the studies are discussed, and recommendations are made to improve the informativeness of studies in the future. Where feasible, the conduct of analytical epidemiological studies—in particular, case control studies—with individual estimates of doses to specific organs from internal and external exposures and with individual information on known and possible risk factors for the diseases of interest should provide important information on health risks from low-level chronic radiation exposures. This information can be maximised by the adoption of common study protocols and common dosimetric approaches and by coordination of efforts across countries.

Evasion of Early Cellular Response Mechanisms following Low Level Radiation-induced DNA Damage

DNA damage that is not repaired with high fidelity can lead to chromosomal aberrations or mitotic cell death. To date, it is unclear what factors control the ultimate fate of a cell receiving low levels of DNA damage (i.e. survival at the risk of increased mutation or cell death). We investigated whether DNA damage could be introduced into human cells at a level and frequency that could evade detection by cellular sensors of DNA damage. To achieve this, we exposed cells to equivalent doses of ionizing radiation delivered at either a high dose rate (HDR) or a continuous low dose rate (LDR). We observed reduced activation of the DNA damage sensor ataxia-telangiectasia mutated (ATM) and its downstream target histone H2A variant (H2AX) following LDR compared with HDR exposures in both cancerous and normal human cells. This lack of DNA damage signaling was associated with increased amounts of cell killing following LDR exposures. Increased killing by LDR radiation has been previously termed the "inverse dose rate effect," an effect for which no clear molecular processes have been described. These LDR effects could be abrogated by the preactivation of ATM or simulated in HDR-treated cells by inhibiting ATM function. These data are the first to demonstrate that DNA damage introduced at a reduced rate does not activate the DNA damage sensor ATM and that failure to activate ATM-associated repair pathways contributes to the increased lethality of continuous LDR radiation exposures. This inactivation may reflect one strategy by which cells avoid accumulating mutations as a result of error-prone DNA repair and may have a broad range of implications for carcinogenesis and, potentially, the clinical treatment of solid tumors.

Comparison in vivo Study of Genotoxic Action of High- Versus Very Low Dose-Rate gamma-Irradiation.

The aim of the present study was to compare genotoxicity induced by high- versus very low dose-rate exposure of mice to gamma-radiation within a dose range of 5 to 61 cGy using the single-cell gel electrophoresis (comet) assay and the micronucleus test. CBA/lac male mice were irradiated at a dose rate of 28.2 Gy/h (high dose rate) or 0.07 mGy/h (very low dose rate). The comet assay study on spleen lymphocytes showed that very low dose-rate irradiation resulted in a statistically significant increase in nucleoid relaxation (DNA breaks), starting from a dose of 20 cGy. Further prolongation of exposure time and, hence, increase of a total dose did not, however, lead to further increase in the extent of nucleoid relaxation. Doses of 20 and 61 cGy were equal in inducing DNA breaks in mouse spleen lymphocytes as assayed by the comet assay. Of note, the level of DNA damage by 20-61 cGy doses of chronic irradiation (0.07 mGy/h) was similar to that an induced by an acute (28.2 Gy/h) dose of 14 cGy. The bone marrow micronucleus test revealed that an increase in polychromatic erythrocytes with micronuclei over a background level was induced by very low-level gamma-irradiation with a dose of 61 cGy only, with the extent of the cytogenetic effect being similar to that of 10 cGy high-dose-rate exposure. In summary, presented results support the hypothesis of the nonlinear threshold nature of mutagenic action of chronic low dose-rate irradiation.

Radioadaptive response and genomic instability: a phenotypic dichotomy of genome–environment interaction

There emerged an upsurge of concern on the diverse cellular response to radiation which was new to the existing paradigm of radiobiology. They include adaptive response, genomic instability, bystander effect, pseudocytokine effect and apoptosis. Their molecular mechanism and health consequences are largely unknown. However, accumulated data indicate that they are all cellular manifestations of programmed adaptive mechanism intrinsic to the organisms for the existence of life either by epistatic response to minimize the negative impact (adaptive response) or by remodeling their genome (genomic instability). The cells have efficient damage sensing and signaling mechanisms for dose-dependent blanching cooperated by protein kinase C (PKC), p38 mitogen-activated protein kinase (p38MAPK) and phospholipase C (PLC) with p53 protein as a downstream effector. The signals are transferred to the bystander cells for orchestrated response. For the adaptive response to have an effect in vivo, two hits must be present within a limited time in a cell or a mass of bystander cells. This determines a minimum effective dose rate, below which remodeling of genome in tissue by apoptotic removal of cells with potentially genotoxic damage may be the prevailing mechanism for modulating radiation effect. Dose refractoriness of chromosome aberrations of stem cell origin in human low dose-rate exposures is consistent with this model.

Early effects of low dose-rate radiation on cultured tumor cells.

Low-dose hyperradiosensitivity (HRS) has been found for several cell types after exposure to low doses, < 0.5 Gy, of high dose-rate (typically 50-150 Gy/h) low-LET radiation. HRS precedes the occurrence of a relative resistance for doses above 0.5-1 Gy. A critical question is whether HRS is of importance in radionuclide therapy where the dose-rate is low but the total dose might be high. An indication that cells exposed to low dose-rate can be kept hyperradiosensitive has recently been published. We have in the present study applied cells without (glioma U373MG) and with (glioma U118MG and colon carcinoma HT29) HRS and studied early effects, up to one week, during low dose-rate (LDR), 0.05-0.09 Gy/hours, exposure (total dose after one week: 11.8 +/- 1.5 Gy). The cells were grown on thin foils above a (32)P source placed in a cell culture chamber. Cell number reductions, cell-cycle disturbances, and changed numbers of apoptotic cells were analyzed after continuous LDR exposures. There seemed to be no relation with HRS when the cell number reduction was considered. The U373MG cells, lacking HRS, had the strongest cell number reduction due to a combination of a G(2) block and increased apoptosis. The U118MG and HT29 cells, both having HRS, had surprisingly low cell number reductions. U118MG had only a G(2) block but no increase in apoptosis. HT29 had both a G(2) block and an increase in apoptosis but the apoptosis change was somewhat smaller than for U373MG. Thus, there seemed to be no obvious relation between HRS and early cellular effects when the cells were analyzed after continuous LDR exposure.

Dose and dose rate effect in mutagenesis, teratogenesis and carcinogenesis

In utero exposure to X-rays, 60Co γ-rays, 252Cf neutron, and 3H water resulted in the linear increase of in vivo somatic mutation in PTHTF 1 mice, while tumors were induced in the offspring after the postnatal treatment with tumor promoter. Apparent dose rate effects were observed in X-ray-induced mutation, malformation and tumor. In the young adult mice exposed to 0.4–6.8 Gy of γ-rays at the dose rates from 0.04 to 1189 mGy/min at the same age, a large and significant reduction of leukemia was observed by the low dose rate exposure, while dose rate effects were not detected in solid tumors at high doses. However, a significant reduction in the incidences of solid tumors was observed at low dose (0.4 Gy) and low dose rate (0.04 mGy/min) exposure. Double-strand break repair deficient SCID (severe combined immunodeficient) mice were extremely sensitive to radiation, and no dose rate effects were observed in γ-ray-induced mortality, malformation and leukemia. The double-strand break repair plays an essential role in homeostasis of the organism. In the normal human tissues maintained in the improved SCID mice, daily UV-light B exposure-induced mutation, keratosis and skin cancer. However, cancer has not been induced in the human thyroid gland below 60 Gy of X-rays, although p53 and c-kit mutations were detected at lower doses.

Studies on the extended Techa river cohort: cancer risk estimation.

Initial population-based studies of riverside residents were begun in the late 1950s and in 1967 a systematic effort was undertaken to develop a well-defined fixed cohort of Techa river residents, to carry out ongoing mortality and (limited) clinical follow-up of this cohort, and to provide individualized dose estimates for cohort members. Over the past decade, extensive efforts have been made to refine the cohort definition and improve both the follow-up and dosimetry data. Analyses of the Techa river cohort can provide useful quantitative estimates of the effects of low dose rate, chronic external and internal exposures on cancer mortality and incidence and non-cancer mortality rates. These risk estimates complement quantitative risk estimates for acute exposures based on the atomic bomb survivors and chronic exposure risk estimates from worker studies, including Mayak workers and other groups with occupational radiation exposures. As the dosimetry and follow-up are refined it may also be possible to gain useful insights into risks associated with 90Sr exposures.

Effect of subsequent acute-dose irradiation on cell survival in vitro following low dose-rate exposures

Purpose : Following acute irradiation, excess radiosensitivity is generally seen at doses <1 Gy, a phenomenon termed 'low-dose hyper-radiosensitivity' (HRS). A very strong, HRS-like inverse dose-rate effect has also been described following continuous low dose-rate (LDR) irradiation at <30 cGy h -1. We report on the sequential irradiation of a cell line by such LDR exposures followed by low acute doses, where either treatment individually would elicit a hypersensitive response. The aim was to determine if a prior LDR exposure would remove the HRS normally seen in response to very small acute radiation doses. Materials and methods : T98G human glioma cells were given single continuous LDR exposures of 5-60 cGy h -1 using a 60 Co γ-source. At intervals of 0 or 4 h following LDR irradiation, cells were further irradiated with a range of acute doses using 240-kVp X-rays. The response to the combined treatment was assessed using high-precision clonogenic cell survival assays, and the amount of HRS at acute doses <1 Gy was determined. Results : LDR at ≥60 cGy h -1 to total doses up to 5 Gy in asynchronously growing cells did not remove HRS in the subsequent acute-dose survival curve. In confluent cultures, subsequent acute-dose HRS was not present after an LDR dose of 5 Gy at either 60 or 30 cGy h -1, but returned if a 4-h interval was left between LDR and acute-dose irradiation. In confluent cultures, acute-dose HRS remained for LDR treatments at 5 or 10 cGy h -1 or if the total dose was 2 Gy. Taking all cultures and dose-rates together, the 'degree' of acute-dose HRS, as measured by α s, was significantly greater in cells irradiated at LDR to a total dose of 2 than of 5Gy. Conclusions : Initial LDR exposure can affect a subsequent HRS response. HRS is reduced after LDR exposures at greater dose intensity, but can recover again within 4 h of completion of LDR exposure. This suggests that processes determining increased resistance to small acute doses (removal of HRS) might be governed by the level of repairable DNA lesions.

Evaluation of the frequencies of chromosomal aberrations in a population exposed to prolonged low dose-rate 60 Co γ-irradiation

Purpose : Chromosomal aberration analysis in peripheral blood lymphocytes was performed to evaluate late cytogenetic effects of long-term low dose-rate γ-irradiation exposure among students and residents exposed in radiocontaminated buildings. Materials and methods : Blood samples were taken from 1913 subjects (age 17.8 ±13.6, mean ±SD) 5-8 years after their relocation from radioactive environments as well as from 176 non-exposed subjects (age 29.6 ±11.9) from the local community. Their lymphocytes were cultured for 48 h and metaphase spreads were prepared. A total of 208 900 metaphases were analysed for different types of chromosomal aberrations. Results : Relatively higher frequencies of translocations (2.1 ×10 -3) , rings (0.6 ×10 -3) and dicentrics (0.6 ×10 -3) were noted in the exposed population as compared with the nonexposed reference populations. Moreover, 356 (78.6%) of the 453 inversions were found on 14q11.2q32 in the exposed population. Among 392 well-demonstrated translocations, 167 (42.6%) and 175 (44.6%) occurred in chromosomes 7 and 14, respectively, while 139 (35.5%) occurred as t(7;14). In particular, the aberrations t(7;14)(p13;q11.2), t(7;14)(p15;q11.2) and t(7;14)(q36;q11.2) were the most prevalent, occurring with frequencies of 19 (13.7%), 20 (14.4%) and 27 (19.4%), respectively. In these, 3205 breakpoints were documented, with chromosomes 7, 9 and 14 shown to carry significantly higher frequencies of breakpoints than expected (≤2 -test, p <0.0001). A further six hotspots were identified on 7p15 (57, 1.8%), 7q36 (42, 1.3%), 9q12 (244, 7.6%), 9q13 (86, 2.7%), 14q11.2 (509, 15.9%) and 14q32 (387, 12.1%) in the exposed population. Conclusion : In comparison with the unexposed population, we observed increased frequencies of various chromosomal aberrations in this human population with previous exposure to prolonged low dose-rate γ-radiation. Moreover, several hotspot breakpoints and inversions and translocations were observed on chromosomes 7 and 14.

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.

Physical heights of children with prolonged low dose-rate γ-radiation exposure in radiocontaminated buildings

Purpose : To evaluate low dose-rate radiation effects on the physical heights of children staying in apartments with 60 Co-contaminated steel construction. Materials and methods : Children who once resided in radiocontaminated apartments since early 1983 were examined for height and body weight status from age 1 month to 18 years and before they moved out of the apartments. The physical heights and body weights of 21 898 age- and sex-matched non-exposed children from a nationwide school surveillance in 1997-98 were taken as controls. The physical height data were shown as height percentiles (HP) compared with reference children and agespecific relative height differences (RHD). Results : HP and RHD in 48 exposed boys and 37 girls were analysed using generalized estimating equations (GEE), which accounted for multiple measurements and correlation between these measurements in the same individuals during this period. After adjusting for effects from parental heights and body mass index (BMI), clear dose-related decreases in HP and RHD were observed in the exposed boys with a cumulative exposure > 60 mSv. Conclusions : Prolonged low dose-rate γ-radiation exposure was associated with adverse effects on the physical heights of growing boys, but were less apparent in the exposed girls.

Radioprotection by Antioxidantsa

The role of reactive oxygen species in ionizing radiation injury and the potential of antioxidants to reduce these deleterious effects have been studied in animal models for more than 50 years. This review focuses on the radioprotective efficacy and the toxicity in mice of phosphorothioates such as WR-2721 and WR-151327, other thiols, and examples of radioprotective antioxidants from other classes of agents. Naturally occurring antioxidants, such as vitamin E and selenium, are less effective radioprotectors than synthetic thiols but may provide a longer window of protection against lethality and other effects of low dose, low-dose rate exposures. Many natural antioxidants have antimutagenic properties that need further examination with respect to long-term radiation effects. Modulation of endogenous antioxidants, such as superoxide dismutase, may be useful in specific radiotherapy protocols. Other drugs, such as nimodipine, propranolol, and methylxanthines, have antioxidant properties in addition to their primary pharmacological activity and may have utility as radioprotectors when administered alone or in combination with phosphorothioates.

Predicting cancer rates in astronauts from animal carcinogenesis studies and cellular markers

The radiation space environment includes particles such as protons and multiple species of heavy ions, with much of the exposure to these radiations occurring at extremely low average dose-rates. Limitations in databases needed to predict cancer hazards in human beings from such radiations are significant and currently do not provide confidence that such predictions are acceptably precise or accurate. In this article, we outline the need for animal carcinogenesis data based on a more sophisticated understanding of the dose–response relationship for induction of cancer and correlative cellular endpoints by representative space radiations. We stress the need for a model that can interrelate human and animal carcinogenesis data with cellular mechanisms. Using a broad model for dose–response patterns which we term the “subalpha–alpha–omega (SAO) model”, we explore examples in the literature for radiation-induced cancer and for radiation-induced cellular events to illustrate the need for data that define the dose–response patterns more precisely over specific dose ranges, with special attention to low dose, low dose-rate exposure. We present data for multiple endpoints in cells, which vary in their radiosensitivity, that also support the proposed model. We have measured induction of complex chromosome aberrations in multiple cell types by two space radiations, Fe-ions and protons, and compared these to photons delivered at high dose-rate or low dose-rate. Our data demonstrate that at least three factors modulate the relative efficacy of Fe-ions compared to photons: (i) intrinsic radiosensitivity of irradiated cells; (ii) dose-rate; and (iii) another unspecified effect perhaps related to reparability of DNA lesions. These factors can produce respectively up to at least 7-, 6- and 3-fold variability. These data demonstrate the need to understand better the role of intrinsic radiosensitivity and dose-rate effects in mammalian cell response to ionizing radiation. Such understanding is critical in extrapolating databases between cellular response, animal carcinogenesis and human carcinogenesis, and we suggest that the SAO model is a useful tool for such extrapolation.

Correcting for exposure measurement error in a reanalysis of lung cancer mortality for the Colorado Plateau Uranium Miners cohort.

The exposure estimates used to date for the analysis of lung cancer mortality in the Colorado Plateau Uranium Miners cohort were developed from radon progeny measurements taken in mines beginning in 1951. Since uranium miners were often exposed over long periods of time and since mines were not continuously monitored, much extrapolation and/or interpolation of measured dose-rates was needed in order to develop estimates of exposure for each of the miners in the cohort. We have recently re-examined the interpolation scheme used to create the histories in the light of the fit of a statistical model for the radon progeny measurements taken in mines within the Plateau, and we have computed revised exposure estimates for the large majority of miners in the cohort. This report describes the use of these new model-based revised exposure estimates in the analysis of lung cancer mortality, using follow-up data current through 1990. Specific issues addressed here are (1) the strength of the association between exposure and risk of lung cancer mortality; (2) effects of attained age and time since exposure upon risk of lung cancer mortality; and (3) exposure-rate effects upon risk. Results using the revised exposure estimates are compared to those obtained fitting the same models using the original Public Health Service (PHS) exposure estimates. We found evidence that the new exposure histories provide a better fit to the lung cancer mortality data than do the histories based upon the original PHS dose-rate estimates. In general, the new results show a stronger overall relationship (larger slope estimate) between lung cancer mortality and exposure per unit exposure compared to those obtained with the original estimates, while displaying similar age at exposure and time since exposure effects. In the reanalysis the impact of low dose-rate exposure is found to be relatively unchanged before and after exposure error correction, while the estimate of the effect of high dose-rate exposure is considerably increased. Even after applying our measurement error corrections, evidence of inverse dose-rate effects is found, since the estimate of the impact of high dose-rate exposure is still below that of the low dose-rates. The magnitude and statistical significance, however, of the dose-rate effect estimates are diminished when fit using the revised exposure estimates.

Ornithine decarboxylase in organs of rat following chronic gamma-irradiation at low dose-rates

Purpose: To investigate the consequence of continuous low doserate exposure to gamma -rays on ornithine decarboxylase (ODC EC 4.1.1.17) activity in organs of rat. Materials and methods: Young male Wistar rats were irradiated at 1.1, 2.1 and 12.9cGy/day in the dose ranges of 9-165, 17-315 and 100-2000cGy, respectively, in a specially designed chamber. ODC activity was determined in 20000g supernatant fluid of thymus, spleen and lung by measuring the release of 14CO from l-{1-14C]ornithine. Results: Chronic gamma-irradiation modulated ODC activity. It decreased at low cumulated doses (after 8 and 15 days of exposure). At longer periods after chronic irradiation (after 45 and 90 days), ODC activity was restored up to control levels despite increasing values of cumulated doses. On day 150 a similar increase in ODC activity in spleen 2.1cGy/day and in lung at 12.9cGy/day was observed. Conclusions: These studies showed a non-monotonic pattern of the 'dose-response' curve. The results were interpreted in terms of the triggering of a homeostatic system.

Dose rate effectiveness and potentially lethal damage repair in normal and double-strand break repair deficient murine cells by γ-rays and 5-fluorouracil

SCID (severe combined immunodeficiency) fibroblasts established from C.B17- scid/ scid embryos showed higher sensitivity to high (1.105 Gy/min) and low (0.00069 Gy/min) dose rate γ-rays and also to 5-fluorouracil, a cancer sedative producing double-strand breaks, than wildtype cells from C.B17-+/+ embryos. Furthermore, SCID cells were deficient in repairing DNA damage induced by high dose rate γ-rays even after dose fractionation and after 24 h recovery periods, while wildtype cells showed an apparent repair ability on DNA damage after these γ-ray exposures. This is the first report to prove that SCID cells lack the repair of γ-ray-induced potentially lethal damage and also of 5-fluorouracil-induced double-strand breaks. However, SCID cells showed a significantly higher survival rate by low dose rate exposure than by high dose rate exposure as in the case of wildtype cells, indicating that SCID cells have a deficiency in DNA repair for high dose rate γ-rays, but not for low dose rate exposure. This suggests an important finding that the dose rate effect (diminution of cell killing by low dose rate exposure) is caused not only by the repair of double-strand breaks induced by γ-rays but in most parts by less yields of double-strand breaks due to dispersed or low intensity ionization in the cell.

Emphasis of biological research for space radiation

The paper summarized issues, current status and the recent topics in biological research of space radiation. Researches to estimate a risk associated with space radiation exposure during a long-term manned space flight, such as in the International Space Station, is emphasized because of the large uncertainty of biological effects and a complexity of the radiation environment in space. The Issues addressed are; 1) biological effects and end points in low dose radiation, 2) biological effects under low dose rate and long-term radiation exposure, 3) modification of biological responses to radiation under space environments, 4) various aspects of biological end points vs. cellular and molecular mechanisms, 5) estimation of human risk associated with radiation exposure in space flight, 6) regulations for radiation exposure limits for space workers. The paper also summarized and introduced recent progress in space related radiation researches with various biological systems.

Continuous, pulsed or single acute irradiation of a transplanted rodent tumour model

Background: Recent advances in remote afterloading pulsed mode brachytherapy have provided a much needed tool for the radiation oncologist. It has the versatility of optimised physical dose distribution along with improved staff radiation protection and patient nursing. Purpose: This preliminary study was designed to explore the radiobiological equivalence between conventional continuous low dose rate tumour irradiation (CLDR) and the new technique of pulsed dose irradiation (PDR). Materials and methods: Subcutaneous isogenic sarcomas transplanted in female John's Strain Wistar rats were irradiated locally with acute, pulsed or continuous interstitial low dose-rate exposures at 9–11 mm mean diameter. Results: As expected, single acute doses (5–40 Gy) were more effective ( P < 0.01) in achieving tumour growth delay (1.4 days/Gy) than CLDR exposure (4–51 Gy) over 24–48 h (0.93 days/Gy). However, PDR treatment (8 hourly fractions/day) at high dose-rate (8–48Gy) over 8–72 h was significantly ( P = 0.01) more effective (1.66 days/Gy) than CLDR but not acute exposures. Conclusions: These data suggest that, clinically a significantly improved therapeutic ratio may also be achievable with pulsed high dose rate brachytherapy, and that further radiobiological studies with in-vivo tumour models are needed.

Radiation risk estimation in human populations: Lessons from the radiological accident in Brazil

The development of radiological and nuclear technologies and the deployment of nuclear weapons have made ionizing radiation one of the most studied human mutagens. Exposure to ionizing radiation produces DNA damage which can result in mutation and cancer, making the risk associated with human exposure a critical issue. In this paper we estimate the risk associated with radiation exposure for individuals exposed to 137Cs during the 1987 Goiânia radiological accident. Using combined regression slopes from both the in vivo hprt mutant frequency and micronucleus frequency data we estimated a doubling dose of 173 (±47) cGy for these two endpoints. This is in close agreement with the published estimates for low dose rate and chronic exposure to low-LET radiation. We obtained risk estimates of about 24-fold increase in dominant disorders in the post-exposure generation of the directly exposed population. No detectable increase was found in the population at large. The risk of carcinogenesis in the directly exposed population was found to be increased by a factor in the range of 1.4 to 1.5. The small sample size in this study requires a large element of caution with respect to risk estimates interpretation. Moreover, the doubling dose estimates prepared here are derived from lymphocytes. This somatic data may require additional considerations for both cancer and certainly germ-line events. Nevertheless, the risk of carcinogenesis and genetic harm for this population are good indicators of the potential genetic damage imposed by ionizing radiation to the Goiânia population.