Why Low-level Radiation Exposure Should Not Be Feared.

ABSTRACT: The purpose of this paper is to address the public fear that is usually associated with low-level radiation exposure situations. Its ultimate objective is to provide persuasive assurances to informed but skeptical members of the public that exposure situations involving low-level radiation are not to be feared. Unfortunately, just acquiescing to an unsupportive public fear of low-level radiation is not without consequences. It is causing severe disruptions to the benefits that harnessed radiation can produce for the well-being of all humanity. In this pursuit, the paper provides the scientific and epistemological basis needed for regulatory reform by reviewing the history in quantifying, understanding, modeling, and controlling radiation exposure, including some of the evolving contributions of the United Nations Scientific Committee on the Effects of Atomic Radiation, the International Commission on Radiological Protection, and the myriad of international and intergovernmental organizations establishing radiation safety standards. It also explores the various interpretations of the linear no-threshold model and the insights gained from radiation pathologists, radiation epidemiologists, radiation biologists, and radiation protectionists. Given that the linear no-threshold model is so deeply imbedded in current radiation exposure guidance, despite the lack of a solid scientific base on the actually proven radiation effects at low-doses, the paper suggests near-term ways to improve regulatory implementation and better serve the public by excluding and/or exempting trivial low-dose situations from the regulatory scope. Several examples are given where the unsubstantiated public fear of low-level radiation has resulted in crippling the beneficial effects that controlled radiation offers to a modern society.

Low-dose radioimmuno-therapy of cancer.

Four decades of genomic, cellular, animal and human data have shown that low-dose ionizing radiation stimulates positive genomic and cellular responses associated with effective cancer prevention and therapy and increased life span of mammals and humans.( 1-8) Nevertheless, this data is questioned because it seems to contradict the well demonstrated linear relation between ionizing radiation dose and damage to DNA without providing a clear mechanistic explanation of how low-dose radiation could produce such beneficial effects. This apparent contradiction is dispelled by current radiobiology that now includes DNA damage both from ionizing radiation and from endogenous metabolic free radicals, and coupled with the biological response to low-dose radiation. Acceptance of current radiobiology would invalidate long established recommendations and regulations of worldwide radiation safety organizations and so destroy the basis of the very expensive existing system of regulation and remediation. More importantly, current radiobiology would facilitate urgently needed clinical trials of low dose radiation (LDR) cancer therapy.

Whole-body responses to low-level radiation exposure: new concepts in mammalian radiobiology.

This review of low dose-induced whole-body effects, especially cancer, shows: 1) Biological systems appear in hierarchy levels of organization, from atoms to molecules, to cells, to tissues and organs, to the whole system; 2) System responses to low-level exposures depend on: quality and number of energy depositions in tissue micromasses (microdoses) being potential triggers to damage and protection; time interval between two microdose events per exposed micromass, that determines cellular responses to the preceding microdose; and responses to microdose events in the system being the target, with the balance between damage and benefit determining the net effect; 3) System responses to acute or chronic low-level exposures evolve from damage to the basic molecular level, mainly to DNA of stem cells, and from adaptive responses that may occur in the whole body. Damage may propagate to successive higher levels of organization, meeting protective barriers which may become upregulated by adaptive responses. The balance between damage and protection at each level per individual depends on tissue dose. At single tissue doses below congruent with 0.1 Gy net benefit tends to outweigh detriment. Thus, progression of damage to clinical disease is not linear; 4) Quality and extent of system responses are under genetic control. Thus, system net responses expectedly vary among individuals; 5) The balance between health risk and benefit of low-level exposure for a given individual may become predictable by gene-expression profiles in control and irradiated cells of this individual; and 6) Clinical trials applying individualized low-level irradiation are justified.

Tissue-sparing effect of x-ray microplanar beams particularly in the CNS: is a bystander effect involved?

OBJECTIVE: Normal tissues, including the central nervous system, tolerate single exposures to narrow planes of synchrotron-generated x-rays (microplanar beams; microbeams) up to several hundred Gy. The repairs apparently involve the microvasculature and the glial system. We evaluate a hypothesis on the involvement of bystander effects in these repairs. METHODS: Confluent cultures of bovine aortic endothelial cells were irradiated with three parallel 27-microm microbeams at 24 Gy. Rats' spinal cords were transaxially irradiated with a single microplanar beam, 270 microm thick, at 750 Gy; the dose distribution in tissue was calculated. RESULTS: Within 6 hours following irradiation of the cell culture the hit cells died, apparently by apoptosis, were lost, and the confluency was maintained. The spinal cord study revealed a loss of oligodendrocytes, astrocytes, and myelin in 2 weeks, but by 3 months repopulation and remyelination was nearly complete. Monte Carlo simulations showed that the microbeam dose fell from the peak's 80% to 20% in 9 microm. CONCLUSIONS: In both studies the repair processes could have involved "beneficial" bystander effects leading to tissue restoration, most likely through the release of growth factors, such as cytokines, and the initiation of cell-signaling cascades. In cell culture these events could have promoted fast disappearance of the hit cells and fast structural response of the surviving neighboring cells, while in the spinal cord study similar events could have been promoting angiogenesis to replace damaged capillary blood vessels, and proliferation, migration, and differentiation of the progenitor glial cells to produce new, mature, and functional glial cells.

Biological Effects From Low Doses and Dose Rates of Ionizing Radiation: Science in the Service of Protecting Humans, a Synopsis.

There is considerable controversy regarding risk of health detriment after low-level exposure to ionizing radiation. This stems in part from a sort of distance between radiation biologists, epidemiologists, and radiation protection professionals, as well as regulatory institutions. Also, there is a lack of overview of the relevant data and their origins regarding health risks at low doses of ionizing radiation. This feeds seriously into a somewhat hazy fear of ionizing radiation that besets large portions of the public. The current synopsis aims at presenting a holistic view in a concise yet comprehensive manner in order to help people understand the full extent of inputs into attempting to relate low-dose radiation exposure to health risk. It emerges again that different approaches must be found for optimal radiation protection replacing the use of the linear no-threshold (LNT) model.

Evidence of a Dose-Rate Threshold for Life Span Reduction of Dogs Exposed Lifelong to γ-Radiation.

Our return to a study on dogs exposed lifelong to cobalt-60 γ-radiation was prompted by a comment that data in dog studies have large statistical errors due to the small number of dogs. We located an earlier article on the same study that had a better mortality curve for the dogs in each dose-rate group. The median life span of the dogs in each group was tabulated, and the standard error of each was calculated. No statistically significant shortening of median life span was observed for the lowest dose-rate group at any reasonable significance level (P value: .005-.05), whereas for dogs with higher irradiation rates, life span shortening was statistically significant at highest reasonable significance level (P value: .005). The results were entered on a graph of life span versus dose rate, assuming a threshold dose-response model. The fitted line indicates that the dose-rate threshold for γ-radiation induced life span reduction is about 600 mGy per year, which is close to the value we found previously. Making allowance for the calculated standard errors, we conclude that this threshold is in the range from 300 to 1100 mGy per year. This evidence is relevant for emergency measures actions (evacuation of residents) and for nuclear waste management.

Radiation Hormesis: The Link to Nanomolar Hydrogen Peroxide.

Hydrogen peroxide (H2O2) is a stable product of water radiolysis, occurring at nanomolar concentration upon low-dose ionizing radiation (LDIR) (<100 mGy). In view of the recent recognition of H2O2 as a central redox signaling molecule that, likewise, is maintained in the nanomolar range in cells, we propose a role for H2O2 in radiation hormesis. LDIR is capable of utilizing known molecular redox master switches such as Nrf2/Keap1 or NF-κB/IκB to effect adaptive resistance. This leads to the hypothesis that, as a normal component of the exposome, LDIR mediates hormetic effects by H2O2 signaling. Antioxid. Redox Signal. 27, 596-598.

Evidence That Lifelong Low Dose Rates of Ionizing Radiation Increase Lifespan in Long- and Short-Lived Dogs.

After the 1956 radiation scare to stop weapons testing, studies focused on cancer induction by low-level radiation. Concern has shifted to protecting "radiation-sensitive individuals." Since longevity is a measure of health impact, this analysis reexamined data to compare the effect of dose rate on the lifespans of short-lived (5% and 10% mortality) dogs and on the lifespans of dogs at 50% mortality. The data came from 2 large-scale studies. One exposed 10 groups to different γ dose rates; the other exposed 8 groups to different lung burdens of plutonium. Reexamination indicated that normalized lifespans increased more for short-lived dogs than for average dogs, when radiation was moderately above background. This was apparent by interpolating between the lifespans of nonirradiated dogs and exposed dogs. The optimum lifespan increase appeared at 50 mGy/y. The threshold for harm (decreased lifespan) was 700 mGy/y for 50% mortality dogs and 1100 mGy/y for short-lived dogs. For inhaled α-emitting particulates, longevity was remarkably increased for short-lived dogs below the threshold for harm. Short-lived dogs seem more radiosensitive than average dogs and they benefit more from low radiation. If dogs model humans, this evidence would support a change to radiation protection policy. Maintaining exposures "as low as reasonably achievable" (ALARA) appears questionable.

Quantification of Adaptive Protection Following Low-dose Irradiation.

The question whether low doses and low dose-rates of ionizing radiation pose a health risk to people is of public, scientific and regulatory concern. It is a subject of intense debate and causes much fear. The controversy is to what extent low-dose effects, if any, cause or protect against damage such as cancer. Even if immediate molecular damage in exposed biological systems rises linearly with the number of energy deposition events (i.e., with absorbed dose), the response of the whole biological system to that damage is not linear. To understand how initial molecular damage affects a complex living system is the current challenge.

The quest to exploit the Auger effect in cancer radiotherapy - a reflective review.

To identify the emergence of the recognition of the potential of the Auger effect for clinical application, and after tracing the salient milestones towards that goal, to evaluate the status quo and future prospects. It was not until 40 years after the discovery of Auger electrons, that the availability of radioactive DNA precursors enabled the biological power, and the clinical potential, of the Auger effect to be appreciated. Important milestones on the path to clinical translation have been identified and reached, but hurdles remain. Nevertheless the potential is still evident, and there is reasonable optimism that the goal of clinical translation is achievable.

Commentary on Inhaled (239)PUO2 in Dogs - A Prophylaxis Against Lung Cancer?

Several studies on the effect of inhaled plutonium-dioxide particulates and the incidence of lung tumors in dogs reveal beneficial effects when the cumulative alpha-radiation dose is low. There is a threshold at an exposure level of about 100 cGy for excess tumor incidence and reduced lifespan. The observations conform to the expectations of the radiation hormesis dose-response model and contradict the predictions of the LNT hypothesis. These studies suggest investigating the possibility of employing low-dose alpha-radiation, such as from (239)PuO2 inhalation, as a prophylaxis against lung cancer.

Cancer Mortality Among People Living in Areas With Various Levels of Natural Background Radiation.

There are many places on the earth, where natural background radiation exposures are elevated significantly above about 2.5 mSv/year. The studies of health effects on populations living in such places are crucially important for understanding the impact of low doses of ionizing radiation. This article critically reviews some recent representative literature that addresses the likelihood of radiation-induced cancer and early childhood death in regions with high natural background radiation. The comparative and Bayesian analysis of the published data shows that the linear no-threshold hypothesis does not likely explain the results of these recent studies, whereas they favor the model of threshold or hormesis. Neither cancers nor early childhood deaths positively correlate with dose rates in regions with elevated natural background radiation.

Radiation-induced versus endogenous DNA damage: possible effect of inducible protective responses in mitigating endogenous damage.

Ionizing radiation (IR) causes damage to DNA that is apparently proportional to absorbed dose. The incidence of radiation-induced cancer in humans unequivocally rises with the value of absorbed doses above about 300 mGy, in a seemingly linear fashion. Extrapolation of this linear correlation down to zero-dose constitutes the linear-no-threshold (LNT) hypothesis of radiation-induced cancer incidence. The corresponding dose-risk correlation, however, is questionable at doses lower than 300 mGy. Non-radiation induced DNA damage and, in consequence, oncogenic transformation in non-irradiated cells arises from a variety of sources, mainly from weak endogenous carcinogens such as reactive oxygen species (ROS) as well as from micronutrient deficiencies and environmental toxins. In order to relate the low probability of radiation-induced cancer to the relatively high incidence of non-radiation carcinogenesis, especially at low-dose irradiation, the quantitative and qualitative differences between the DNA damages from non-radiation and radiation sources need to be addressed and put into context of physiological mechanisms of cellular protection. This paper summarizes a co-operative approach by the authors to answer the questions on the quantitative and qualitative DNA damages from non-radiation sources, largely endogenous ROS, and following exposure to low doses of IR. The analysis relies on published data and justified assumptions and considers the physiological capacity of mammalian cells to protect themselves constantly by preventing and repairing DNA damage. Furthermore, damaged cells are susceptible to removal by apoptosis or the immune system. The results suggest that the various forms of non-radiation DNA damage in tissues far outweigh corresponding DNA damage from low-dose radiation exposure at the level of, and well above, background radiation. These data are examined within the context of low-dose radiation induction of cellular signaling that may stimulate cellular protection systems over hours to weeks against accumulation of DNA damage. The particular focus is the hypothesis that these enhanced and persisting protective responses reduce the steady state level of non-radiation DNA damage, thereby reducing deleterious outcomes such as cancer and aging. The emerging model urgently needs rigorous experimental testing, since it suggests, importantly, that the LNT hypothesis is invalid for complex adaptive systems such as mammalian organisms.

Commentary: ethical issues of current health-protection policies on low-dose ionizing radiation.

The linear no-threshold (LNT) model of ionizing-radiation-induced cancer is based on the assumption that every radiation dose increment constitutes increased cancer risk for humans. The risk is hypothesized to increase linearly as the total dose increases. While this model is the basis for radiation safety regulations, its scientific validity has been questioned and debated for many decades. The recent memorandum of the International Commission on Radiological Protection admits that the LNT-model predictions at low doses are "speculative, unproven, undetectable and 'phantom'." Moreover, numerous experimental, ecological, and epidemiological studies show that low doses of sparsely-ionizing or sparsely-ionizing plus highly-ionizing radiation may be beneficial to human health (hormesis/adaptive response). The present LNT-model-based regulations impose excessive costs on the society. For example, the median-cost medical program is 5000 times more cost-efficient in saving lives than controlling radiation emissions. There are also lives lost: e.g., following Fukushima accident, more than 1000 disaster-related yet non-radiogenic premature deaths were officially registered among the population evacuated due to radiation concerns. Additional negative impacts of LNT-model-inspired radiophobia include: refusal of some patients to undergo potentially life-saving medical imaging; discouragement of the study of low-dose radiation therapies; motivation for radiological terrorism and promotion of nuclear proliferation.