On the general validity of linear summation of dose equivalents for mixed radiations

The current definition of dose equivalent for a mixture of radiations used in radiation protection implies some interaction between the radiations. This interaction cannot be derived from the existing biophysical models. A simple concept of interaction is introduced based on the postulate that in the chain of radiation inactivation events, there exists an intermediate stage where different initial lesions, produced by different radiations, become functionally indistinguishable. Hence, they are additive thereafter to produce the same end point observed. It can be shown that the definition of dose equivalent and the definition of average quality factors for mixed radiations can be derived from this concept. Furthermore, this simple concept can be shown to be consistent with many of the published experimental results in radiobiology using mixed radiations. The lesion additivity concept helps to provide both theoretical and experimental support for the otherwise arbitrary definitions of dose equivalent and average quality factor.     

Epidemiological evaluation of radiation risk using populations exposed at high doses

Reasons are discussed for basing cancer risk estimates of low-dose radiation effects on extrapolations from populations exposed to high doses, rather than directly on studies of low-dose effects. Some of the major studies used for this purpose are described, together with difficulties encountered in extrapolating from them. Some recent statistical work to aid the evaluation of radiation risk from these studies is reviewed.     

Biological effects of cosmic radiation: deterministic and stochastic

Our basic understanding of the biological responses to cosmic radiations comes in large part from an international series of ground-based laboratory studies, where accelerators have provided the source of representative charged particle radiations. Most of the experimental studies have been performed using acute exposures to a single radiation type at relatively high doses and dose rates. However, most exposures in flight occur from low doses of mixed radiation fields at low-dose rates. This paper provides a brief overview of existing pertinent clinical and biological radiation data and the limitations associated with data available from specific components of the radiation fields in airflight and space travel.     

What is hormesis and why haven't we heard about it before?

Low doses of ionizing radiation are widely believed to produce effects similar to those observed at high doses; only the incidence (i.e. risk) varies with dose. Furthermore, it is assumed that effects other than those observed at high doses will not occur at low doses. Yet there have been frequent reports in the literature of "anomalies" at low doses--effects unrelated to and unpredictable from the high-dose exposure experiences. These have been referred to as "hormetic" effects. These effects have their parallel with other hormetic effects seen with many other agents generally considered toxic. It is postulated that hormesis has previously received scant attention because it conflicts with the conventional radiation science paradigm.     

Energy dependence of dose and dose-rate effectiveness factor for low-let radiations: potential importance to estimation of cancer risks and relationship to biological effectiveness

A dose and dose-rate effectiveness factor (DDREF) for low-linear energy transfer (LET) radiations (photons and electrons) is used in cancer risk assessments to represent an assumption that risks at low doses and low dose rates may be less than estimates that are based mainly on linear extrapolations of observed risks at higher acute doses. DDREF generally is assumed to be independent of energy. However, a variety of radiobiological data reviewed in this paper suggest that DDREF may decrease with decreasing energy. This effect, which parallels increases in biological effectiveness with decreasing energy of photons and electrons that have been observed in many radiobiological studies, has received little attention. The importance of an overestimation of DDREF at low energies of photons and electrons is that cancer risks at low doses and low dose rates could be underestimated. This paper also discusses (1) the link between DDREF and the usual assumption of a linear-quadratic dose-response relationship for low-LET radiations and (2) concerns about the validity of estimates of DDREF and biological effectiveness used in cancer risk assessments that are raised by results of recent studies that cast doubt on whether the underlying radiobiological data can be represented by a simple linear-quadratic model.     

Energy-dependent RBE of neutrons to induce micronuclei in root-tip cells of Allium cepa onion irradiated as dry dormant seeds and seedlings

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

Mechanisms and biological importance of photon-induced bystander responses: do they have an impact on low-dose radiation responses

Elucidating the biological effect of low linear energy transfer (LET), low-dose and/or low-dose-rate ionizing radiation is essential in ensuring radiation safety. Over the past two decades, non-targeted effects, which are not only a direct consequence of radiation-induced initial lesions produced in cellular DNA but also of intra- and inter-cellular communications involving both targeted and non-targeted cells, have been reported and are currently defining a new paradigm in radiation biology. These effects include radiation-induced adaptive response, low-dose hypersensitivity, genomic instability, and radiation-induced bystander response (RIBR). RIBR is generally defined as a cellular response that is induced in non-irradiated cells that receive bystander signals from directly irradiated cells. RIBR could thus play an important biological role in low-dose irradiation conditions. However, this suggestion was mainly based on findings obtained using high-LET charged-particle radiations. The human population (especially the Japanese, who are exposed to lower doses of radon than the world average) is more frequently exposed to low-LET photons (X-rays or γ-rays) than to high-LET charged-particle radiation on a daily basis. There are currently a growing number of reports describing a distinguishing feature between photon-induced bystander response and high-LET RIBR. In particular, photon-induced bystander response is strongly influenced by irradiation dose, the irradiated region of the targeted cells, and p53 status. The present review focuses on the photon-induced bystander response, and discusses its impact on the low-dose radiation effect.     

Overview of radiation environments and human exposures

Human exposures to ionizing radiation have been vastly altered by developing technology in the last century. This has been most obvious in the development of radiation generating devices and the utilization of nuclear energy. But even air travel has had its impact on human exposure. Human exposure increases with advancing aircraft technology as a result of the higher operating altitudes reducing the protective cover provided by Earth's atmosphere from extraterrestrial radiations. This increase in operating altitudes is taken to a limit by human operations in space. Less obvious is the changing character of the radiations at higher altitudes. The associated health risks are less understood with increasing altitude due to the increasing complexity and new field components found in high-altitude and space operations.     

The historical and current application of the FIB-1 model to assess organ dose from plutonium intakes in Mayak workers

One of the objectives of the Joint Coordinating Committee for Radiation Effects Research Project 2.4 is to document the methodology used to determine the radiation doses in workers from the Mayak Production Association who were exposed to plutonium. The doses have been employed in numerous dose response studies measuring both stochastic and deterministic effects. This article documents both the historical (pre-1999) and current ("Doses 1999") methods used by the FIB-1 scientists to determine the doses. Both methods are based on a three-chamber lung model developed by the FIB-1 scientists. This method was developed in partial isolation from the West and has unique characteristics from the more familiar ICRP biokinetic models. Some of these characteristics are the use of empirically based transportability classifications and the parameter modification for chelation-therapy-enhanced excretion data. An example dose calculation is provided and compared to the dose that would be obtained if the ICRP models were used. The comparison demonstrates that the models are not interchangeable and produce different results.     

Radon exposure of the skin: I. Biological effects.

Radon progeny can plate out on skin and give rise to exposure of the superficial epidermis from alpha emitters Po-218 (7.7 MeV, range approximately 66 microm) and Po-214 (6 MeV, range approximately 44 microm). Dose rates from beta/gamma emitters Pb-214 and Bi-214 are low and only predominate at depths in excess of the alpha range. This paper reviews the evidence for a causal link between exposure from radon and its progeny, and deterministic and stochastic biological effects in human skin.Radiation induced skin effects such as ulceration and dermal atrophy, which require irradiation of the dermis, are ruled out for alpha irradiation from radon progeny because the target cells are considerably deeper than the range of alpha particles. They have not been observed in man or animals. Effects such as erythema and acute epidermal necrosis have been observed in a few cases of very high dose alpha particle exposures in man and after acute high dose exposure in animals from low energy beta radiations with similar depth doses to radon progeny. The required skin surface absorbed doses are in excess of 100 Gy. Such effects would require extremely high levels of radon progeny. They would involve quite exceptional circumstances, way outside the normal range of radon exposures in man.There is no definitive identification of the target cells for skin cancer induction in animals or man. The stem cells in the basal layer which maintain the epidermis are the most plausible contenders for target cells. The majority of these cells are near the end of the range of radon progeny alpha particles, even on the thinnest body sites. The nominal depth of these cells, as recommended by the International Commission on Radiological Protection (ICRP), is 70 microm. There is evidence however that some irradiation of the hair follicles and/or the deeper dermis, as well as the inter-follicular epidermis, is also necessary for skin cancer induction. Alpha irradiation of rodent skin that is restricted to the epidermis does not produce skin cancer. Accelerator generated high energy helium and heavy ions can produce skin cancer in rodents at high doses, but only if they penetrate deep into the dermis. The risk figures for radiation induced skin cancer in man recommended by the ICRP in 1990 are based largely on x and beta irradiated cohorts, but few data exist below absorbed doses of about 1 Gy. The only plausible finding of alpha-radiation induced skin cancer in man is restricted to one study in Czech uranium miners. There is no evidence in other uranium miners and the Czech study has a number of shortcomings.This review concludes that the overall balance of evidence is against causality of radon progeny exposure and skin cancer induction. Of particular relevance is the finding in animal studies that radiation exposure of cells which are deeper than the inter-follicular epidermis is necessary to elicit skin cancer. In spite of this conclusion, a follow-on paper evaluates the attributable risk of radon to skin cancer in the UK on the basis that target cells for skin cancer induction are the cells in the basal layer of the inter-follicular epidermis-since this is the conservative assumption made by international bodies such as the International Commission on Radiological Protection (ICRP) for general radiological protection purposes.     

Formation of clustered DNA damage after high-LET irradiation: a review

Radiation can cause as well as cure cancer. The risk of developing radiation-induced cancer has traditionally been estimated from cancer incidence among survivors of the atomic bombs in Hiroshima and Nagasaki.(1)) These data provide the best estimate of human cancer risk over the dose range for low linear energy transfer (LET) radiations, such as X- or gamma-rays. The situation of estimating the real biological effects becomes even more difficult in the case of high LET particles encountered in space or as the result of domestic exposure to alpha-particles from radon gas emitters or other radioactive emitters like uranium-238.Complex DNA damage, i.e., the signature of high-LET radiations comprises of closely spaced DNA lesions forming a cluster of DNA damage. The two basic groups of complex DNA damage are double strand breaks (DSBs) and non-DSB oxidative clustered DNA lesions (OCDL). Theoretical analysis and experimental evidence suggest an increased complexity and severity of complex DNA damage with increasing LET (linear energy transfer) and a high mutagenic or carcinogenic potential. Data available on the formation of clustered DNA damage (DSBs and OCDL) by high-LET radiations are often controversial suggesting a variable response to dose and type of radiation. The chemical nature and cellular repair mechanisms of complex DNA damage have been much less characterized than those of isolated DNA lesions like an oxidized base or a single strand break especially in the case of high-LET radiation. This review will focus on the induction of clustered DNA damage by high-LET radiations presenting the earlier and recent relative data.     

Nested case-control study of external ionizing radiation dose and mortality from dementia within a pooled cohort of female nuclear weapons workers

BACKGROUND: A prior investigation of this cohort of female nuclear workers found increased deaths from mental disorders, including dementia. The present study estimates the effect of workplace exposures to ionizing radiations and other hazards on mortality from dementia. METHODS: A nested case-control study within a pooled cohort of 67,976 female nuclear workers compared 91 cases of death from dementia with 910 controls. Adjusted odds ratios (ORs) were employed to estimate the effects of maximum annual and total lifetime radiation doses on the occurrence of dementia in 168 monitored workers. RESULTS: Both maximum annual (OR = 2.11, 95% confidence interval (CI) = 0.98, 4.40) and total lifetime radiation doses (OR = 2.09, 95% CI = 1.02, 4.29) were associated with death from dementia. Significant dose-response trends were present for both exposures. CONCLUSIONS: Occupational exposure to ionizing radiation (IR) may be associated with increased risk of death from dementia in female workers. Since these findings are based on a small number of cases, replication with a larger case sample should be pursued.     

Prematurely condensed chromosome rings after neutron irradiation of human lymphocytes

Calibration curves for fission spectrum neutrons and other high LET radiations are scarce in cytogenetic dosimetry and particularly for Prematurely Condensed Chromosome Rings (PCC-ring). Here we analyzed the behavior of the PCC-ring frequency and PCC index after neutron irradiation in a broad dose interval from 1 to 26 Gy. PCC-rings were induced in lymphocytes with Calyculin A. 6455 PCC cells in G1, G2/M and M/A stages were analyzed. The best fitting between the frequency of PCC ring (Y) and the Dose (D) was obtained with the equation Y = (0.059 ± 0.003) D. The saturation of the PCC-ring was observed after around 4 Gy, but it was still possible to analyze cells exposed up to 26 Gy. The distribution of rings by cell follows Poisson or Neyman type distribution for all doses. This PCC-ring dose effect curve can be used in case of accidental overexposure to neutron radiation, allowing a dose assessment in a reliable way. Additionally, the PCC index seems to be well correlated with radiation dose and decrease in a dose dependent manner from 13% in non exposed sample down to 0.2%. This observation allows the possibility to perform a quick classification of victims exposed to high doses of both gamma and neutron radiations. The PCC assay can then be used for both neutron dose estimation up to 4 Gy and for the rapid classification of victims exposed to higher doses. This assay could be included in the multiparametric approach developed to optimize the medical treatment of radiation victims.     

Radiation biology: concepts for radiation protection

The opportunity to write a historical review of the field of radiation biology allows for the viewing of the development and maturity of a field of study, thereby being able to provide the appropriate context for the earlier years of research and its findings. The pioneering work of Muller, Sax, and McClintock, and many others, has stood the test of time. The idea that x-rays could damage the genetic material and result in interactions that could lead to gene mutations and a range of chromosomal alterations is now interpretable in terms of induced DNA damage and errors of DNA repair. The expanded idea that such genetic alterations can be induced by DNA damage that is produced by one or two tracks of ionizing radiation remains the mainstay of radiation biology. The impact of the more recent molecular approaches to unraveling the mechanism behind this simple concept has confirmed this fundamental observation. The remarkable advances have allowed for a fairly complete understanding of the specific types of DNA damage induced by ionizing radiations and the pivotal role played by the errors of repair of double-strand breaks. Given our considerably enhanced knowledge of the details of the DNA repair processes involved, misrepair is a very unlikely event. The role of potential confounders of the concept of dose-response (e.g., bystander effects, genomic instability, and adaptive responses) is taking on a growing importance to the field. The evolving need is to begin to consider mechanistically-based dose-response models for cancer risk such that any potential impact of confounders on the response at low, environmental doses can be assessed. Thus, radiation biology research has always had a focus on how best to protect human health from radiation exposures and will continue to do so.     

Estimate of doses to the fetus during commercial flights

This study assesses the radiation exposure from cosmic rays to fetuses of pregnant aircrew and air travelers. Combining the particle fluence spectra of various cosmic radiations at aircraft altitudes with the fetal fluence-to-dose conversion coefficients calculated for different cosmic ray radiations, the doses to the fetal body were estimated for three prenatal ages. From the five major particle types present during commercial flights, neutrons contribute about 54% of the total fetal dose, followed by protons 22%, photons 11%, electrons 7%, and muons 6%. The results indicate that the dose to the fetus can exceed a recommended fetal dose limit of 1 mSv after 10 round trips on commercial flights between Toronto and Frankfurt.     

Radiation biology: concepts for radiation protection

The opportunity to write a historical review of the field of radiation biology allows for the viewing of the development and maturity of a field of study, thereby being able to provide the appropriate context for the earlier years of research and its findings. The pioneering work of Muller, Sax, and McClintock, and many others, has stood the test of time. The idea that x-rays could damage the genetic material and result in interactions that could lead to gene mutations and a range of chromosomal alterations is now interpretable in terms of induced DNA damage and errors of DNA repair. The expanded idea that such genetic alterations can be induced by DNA damage that is produced by one or two tracks of ionizing radiation remains the mainstay of radiation biology. The impact of the more recent molecular approaches to unraveling the mechanism behind this simple concept has confirmed this fundamental observation. The remarkable advances have allowed for a fairly complete understanding of the specific types of DNA damage induced by ionizing radiations and the pivotal role played by the errors of repair of double-strand breaks. Given our considerably enhanced knowledge of the details of the DNA repair processes involved, misrepair is a very unlikely event. The role of potential confounders of the concept of dose-response (e.g., bystander effects, genomic instability, and adaptive responses) is taking on a growing importance to the field. The evolving need is to begin to consider mechanistically-based dose-response models for cancer risk such that any potential impact of confounders on the response at low, environmental doses can be assessed. Thus, radiation biology research has always had a focus on how best to protect human health from radiation exposures and will continue to do so.     

Effect of the administration of bismuth nitrate on radiogenic thymoma induction in mice.

Metallothionein functions as a radical scavenger protecting cells from the indirect effect of radiations. We investigated the effect of bismuth nitrate, an efficient inducer of metallothionein, on acute and late effects of radiation in mice. Metallothionein contents were examined in several organs after the administration of bismuth nitrate. The content in bone marrow increased 2-fold in the treated as compared to the control mice. This treatment protected irradiated mice from bone marrow death and increased the number of endogenous spleen colonies. The metallothionein content in the ileum did not change after treatment with bismuth nitrate. Mice were not protected by bismuth nitrate when exposed to 9 Gy of X-rays. This suggests that this agent does not protect from gastrointestinal death. The incidence of X-ray-induced thymic lymphomas was lowered by the administration of bismuth nitrate in mice exposed to four fractionated doses of 1.3 Gy of X-rays. These results indicate that bismuth nitrate effectively modified both acute and late effects of X-rays by inducing metallothionein in the target tissues.     

Reconstruction of external dose from beta radiation sources of nuclear weapon origin

In response to requests from the Department of Veterans Affairs, a methodology was developed to assess the external dose accrued by personnel in the vicinity of beta radiation sources of nuclear weapon origin. This methodology has been applied in support of the Nuclear Test Personnel Review (NTPR) Program implemented by the Department of Defense. As required by the Code of Federal Regulations (Title 32, Part 218 and Title 38, Part 3.311), the NTPR Program must evaluate radiological hazards from nuclear testing activities that include alpha particle, beta particle, neutron, and photon emissions from radionuclides. Prior to the development of this methodology, only photon and neutron radiations were explicitly quantified for external dose assessments in this program. Alpha radiation of external origin presents no risk for biological effects due to external dose potential to skin tissue because of the particle's very limited range. However, beta particles are sufficiently penetrating to have such potential. Methods are provided to quantify ionizing radiation doses to the skin and lens of the eye from beta radiation sources of nuclear weapon origin located external to the body. This formulation allows the estimation of beta dose from a film badge (gamma) dose or from an equivalent reconstructed gamma dose.     

Epidemiologic data on radiation-induced breast cancer

BackgroundFemale breast cancer is the most frequent cancer, both in incidence and mortality. It is well known that exposure to ionizing radiation increases the risk, but some questions remain concerning low dose and low-dose rate effects and cofactors. These potential effects have to be taken into account to carry out adequate risk assessment on medically exposed populations. A literature review is proposed on this issue.MethodsA Medline research was undertaken. Keywords used were ionizing radiation, breast cancer and epidemiology. More studies were added through references included in the first list of articles. The focus was placed on studies including quantitative dose–effect relationship analyses.ResultsA latency of five to 10 to 13 years is observed in the appearance of risk. The risk diminishes with age at exposure. A diminution with age at risk is also suspected. The excess relative risk per gray varies between 0.3 and 1.5 for an age at first exposure of 25 years. The study of Hiroshima and Nagasaki survivors shows that risk is increased even if doses are restricted to below 0.5 Gy. Above high doses (20 Gy), the risk no longer increases. This can be interpreted as a cell-killing effect. The excess subsists if doses are fractionated, but a diminution of the effect is suspected.ConclusionThe effects of exposure to levels of doses used for medical diagnostic are very difficult to study in the general population by epidemiological methods. Only studies conducted on very young children could achieve enough power, because of their high radiosensitivity. Available information on the effects of doses above 0.5 Gy allows extrapolation on maximal effects. Models deduced from existing cohorts can be used to assess risk, with their limits due to associated uncertainties. Preston et al. proposed an excess absolute-risk model, which makes estimates from the more comprehensive cohorts compatible. This model has been retained by the 2006 committee “Biological effects of ionizing radiation” (report VII).     

RADFOOD--a dynamic model for radioactivity transfer through the human food chain

Radioactive fallout presents a short-term risk due to its direct deposition on agricultural crops, as well as a long-term risk resulting from its deposition on soil and subsequent uptake by crops. A dynamic model, RADFOOD, was developed, based on different existing models. It simulates transport of fallout radionuclides through agricultural food chains to man and evaluates the radiation doses resulting from consumption of contaminated food. Transport was modeled through compartments representing various environmental elements of food products. Internal radiation doses (whole-body weighted doses) following ingestion of contaminated foodstuffs were then estimated. Specific types of crops, soils and diet of man and livestock were considered. A sample calculation was performed in which individual and collective radiation doses, as well as associated health effects, resulting from fallout contamination were evaluated. They were estimated for food consumption beginning at various times after the fallout deposition and for different consumption durations. A sensitivity analysis, performed for the main model parameters, showed that the radiation dose is sensitive, for the short-term period, to changes in initial deposition levels and in the parameters characterizing initial fallout interception and resuspension.