How the Science of Radiation Biology Can Help Reduce the Crippling Fear of Low-level Radiation.

ABSTRACT: The fear of radiation has been present almost since the discovery of radiation, but has intensified since the "dawn of the atomic age" over 75 y ago. This fear has often served as an impediment to the safe and beneficial uses of radiation and radioactive material. The underlying causes of such fear are varied, can be complex, and are often not associated with any scientific knowledge or understanding. The authors believe that a clear understanding of the current scientific knowledge and understanding of the effects of radiation exposure may be useful in helping to allay some of the fear of radiation. This manuscript attempts to (1) address several scientific questions that we believe have contributed to the fear of radiation, (2) review the data derived from research that can be used to address these questions, and (3) summarize how the results of such scientific research can be used to help address the fear of low-dose and low-dose-rate radiation. Several examples of how fear of radiation has affected public perception of radiological events are discussed, as well as a brief history of the etiology of radiation fear. Actions needed to reduce the public fear of radiation and help fulfill the full societal benefits of radiation and radioactive materials are suggested.

Radiobiology of Select Radionuclides in Hanford Site Tank Waste.

ABSTRACT: There are several important radionuclides involved in the "clean-up" or environmental isolation of nuclear waste contained in US Department of Energy Hanford Site underground waste tanks that drive many of the decisions associated with this activity. To make proper human health risk analyses and ensure that the most appropriate decisions are made, it is important to understand the radiation biology and the human health risk associated with these radionuclides. This manuscript provides some basic radiological science, in particular radiation biology, for some of these radionuclides, i.e., 3 H, 90 Sr, 137 Cs, 99 Tc, 129 I, and the alpha emitters 239, 240 Pu, 233,234,235,238 U, and 241 Am. These radionuclides were selected based on their designation as "constituents of potential concern," historical significance, or potential impact on human health risk. In addition to the radiobiology of these select radionuclides, this manuscript provides brief discussions of the estimated cost of planned management of Hanford tank waste and a comparison with releases into the Techa River from activities associated with the Mayak Production Association. A set of summary conclusions of the potential human health risks associated with these radionuclides is given.

Cost of fear and radiation protection actions: Washington County, Utah and Fukushima, Japan {Comparing case histories}.

Purpose: The purpose of this manuscript is to evaluate the role of regulatory limits and regulatory action on the total impact of nuclear contamination and accidents. While it is important to protect the public from excessive radiation exposures it is also critical to weigh the damage done by implementing regulations against the benefits produced. Two cases: Actions taken as a result of radioactive fallout in Washington County, Utah in 1953 from the atomic bomb testing in Nevada, and the actions implemented post release of radioactive materials into the environment from the damaged nuclear power reactor at Fukushima, Japan, are compared.Materials and methods: The Washington County radiation exposures and doses, resulting from the Nevada nuclear weapons tests, were taken from published reports, papers, and historical records. The protective actions taken were reviewed and reported. Recent publications were used to define the doses following Fukushima. The impact and/or results of sheltering only versus sheltering/evacuation of Washington County and Fukushima are compared.Results: The radiation dose from the fallout in Washington County from the fallout was almost 2-3 three times the dose in Japan, but the regulatory actions were vastly different. In Utah, the minimal action taken, e.g. sheltering in place, had no major impact on the public health or on the economy. The actions in Fukushima resulted in major negative impact precipitated through the fear generated. And the evacuation. The results had adverse human health and wellness consequences and a serious impact on the economy of the Fukushima region, and all of Japan.Conclusions: When evacuation is being considered, great care must be taken when any regulatory actions are initiated based on radiation limits. It is necessary to consider total impact and optimize the actions to limit radiation exposure while minimizing the social, economic, and health impacts. Optimization can help ensure that the protective measures result in more good than harm. It seems clear that organizations who recommend radiation protection guidelines need to revisit the past and current guides in light of the significant Fukushima experience.

The impact of dose rate on the linear no threshold hypothesis.

The goal of this manuscript is to define the role of dose rate and dose protraction on the induction of biological changes at all levels of biological organization. Both total dose and the time frame over which it is delivered are important as the body has great capacity to repair all types of biological damage. The importance of dose rate has been recognized almost from the time that radiation was discovered and has been included in radiation standards as a Dose, Dose Rate, Effectiveness Factor (DDREF) and a Dose Rate Effectiveness Factor (DREF). This manuscript will evaluate the role of dose rate at the molecular, cellular, tissue, experimental animals and humans to demonstrate that dose rate is an important variable in estimating radiation cancer risk and other biological effects. The impact of low-dose rates on the Linear-No-Threshold Hypothesis (LNTH) will be reviewed since if the LNTH is not valid it is not possible to calculate a single value for a DDREF or DREF. Finally, extensive human experience is briefly reviewed to show that the radiation risks are not underestimated and that radiation at environmental levels has limited impact on total human cancer risk.

Re-evaluation of the linear no-threshold (LNT) model using new paradigms and modern molecular studies.

The linear no-threshold (LNT) model is currently used to estimate low dose radiation (LDR) induced health risks. This model lacks safety thresholds and postulates that health risks caused by ionizing radiation is directly proportional to dose. Therefore even the smallest radiation dose has the potential to cause an increase in cancer risk. Advances in LDR biology and cell molecular techniques demonstrate that the LNT model does not appropriately reflect the biology or the health effects at the low dose range. The main pitfall of the LNT model is due to the extrapolation of mutation and DNA damage studies that were conducted at high radiation doses delivered at a high dose-rate. These studies formed the basis of several outdated paradigms that are either incorrect or do not hold for LDR doses. Thus, the goal of this review is to summarize the modern cellular and molecular literature in LDR biology and provide new paradigms that better represent the biological effects in the low dose range. We demonstrate that LDR activates a variety of cellular defense mechanisms including DNA repair systems, programmed cell death (apoptosis), cell cycle arrest, senescence, adaptive memory, bystander effects, epigenetics, immune stimulation, and tumor suppression. The evidence presented in this review reveals that there are minimal health risks (cancer) with LDR exposure, and that a dose higher than some threshold value is necessary to achieve the harmful effects classically observed with high doses of radiation. Knowledge gained from this review can help the radiation protection community in making informed decisions regarding radiation policy and limits.

BEIR VI radon: The rest of the story.

The National Academy of Sciences (USA) conducted an extensive review on the health effects of radon (BEIR VI). This was a well written and researched report which had impact on regulations, laws and remediation of radon in homes. There were a number of problems with the interpretation of the report and three are focused on here. First, most of the radiation dose used to estimate risk was from homes with radon levels below the US Environmental Protection Agency's action level so that remediation had minor impact on total calculated attributable risk. Remediation of the high level homes (i.e., above the action level) would therefore have a minor impact on the calculated "population attributable risk". In individual homes with very high levels of radon, remediation may minimally reduce individual risk. Second, the conclusion communicated to the public, regulators and law makers was "Next to cigarette smoking radon is the second leading cause of lung cancer." This is not an accurate evaluation of the report. The correct conclusion would be: Next to cigarette smoking, high levels of radon combined with cigarette smoking is the second leading cause of lung cancer. In the never-smokers, few cancers could be attributable to radon. Thirdly, there is little question that high levels of radon exposure in mines combined with cigarette smoke and other significant insults in the mine environment produces excess lung cancer. However, the biological responses to low doses of radiation are different from those produced by high levels and low doses may result in unique protective responses (e.g. against smoking-related lung cancer). These three points will be discussed in detail. This paper shows that in contrary to the BEIR VI report, risk of lung cancer from residential radon is not increased and radon in homes appears to be helping to prevent smoking-related lung cancer. Thus, laws requiring remediation of homes for radon are providing little if any public health benefits.

A Critical Assessment of the Linear No-Threshold Hypothesis: Its Validity and Applicability for Use in Risk Assessment and Radiation Protection.

The Society of Nuclear Medicine and Molecular Imaging convened a task group to examine the evidence for the risk of carcinogenesis from low-dose radiation exposure and to assess evidence in the scientific literature related to the overall validity of the linear no-threshold (LNT) hypothesis and its applicability for use in risk assessment and radiation protection. In the low-dose and dose-rate region, the group concluded that the LNT hypothesis is invalid as it is not supported by the available scientific evidence and, instead, is actually refuted by published epidemiology and radiation biology. The task group concluded that the evidence does not support the use of LNT either for risk assessment or radiation protection in the low-dose and dose-rate region.

Funding for radiation research: past, present and future.

For more than a century, ionizing radiation has been indispensable mainly in medicine and industry. Radiation research is a multidisciplinary field that investigates radiation effects. Radiation research was very active in the mid- to late 20th century, but has then faced challenges, during which time funding has fluctuated widely. Here we review historical changes in funding situations in the field of radiation research, particularly in Canada, European Union countries, Japan, South Korea, and the US. We also provide a brief overview of the current situations in education and training in this field. A better understanding of the biological consequences of radiation exposure is becoming more important with increasing public concerns on radiation risks and other radiation literacy. Continued funding for radiation research is needed, and education and training in this field are also important.

The influence of changing dose rate patterns from inhaled beta-gamma emitting radionuclide on lung cancer.

PURPOSE: Dose and dose rate are both appropriate for estimating risk from internally deposited radioactive materials. We investigated the role of dose rate on lung cancer induction in Beagle dogs following a single inhalation of strontium-90 (90Sr), cerium-144 (144Ce), yttrium-91 (91Y), or yttrium-90 (90Y). As retention of the radionuclide is dependent on biological clearance and physical half-life a representative quantity to describe this complex changing dose rate is needed. MATERIALS AND METHODS: Data were obtained from Beagle dog experiments from the Inhalation Toxicology Research Institute. The authors selected the dose rate at the effective half-life of each radionuclide (DRef). RESULTS: Dogs exposed to DRef (1-100 Gy/day) died within the first year after exposure from acute lung disease. Dogs exposed at lower DRef (0.1-10 Gy/day) died of lung cancer. As DRef decreased further (<0.1 Gy/day 90Sr, <0.5 Gy/day 144Ce, <0.9 Gy/day 91Y, <8 Gy/day 90Y), survival and lung cancer frequency were not significantly different from control dogs. CONCLUSION: Radiation exposures resulting from inhalation of beta-gamma emitting radionuclides that decay at different rates based on their effective half-life, leading to different rates of decrease in dose rate and cumulative dose, is less effective in causing cancer than acute low linear energy transfer exposures of the lung.

The Role of Radiation Induced Injury on Lung Cancer.

This manuscript evaluates the role of cell killing, tissue disorganization, and tissue damage on the induction of lung cancer following low dose rate radiation exposures from internally deposited radioactive materials. Beagle dogs were exposed by inhalation to 90Y, 91Y, 144Ce, or 90Sr in fused clay particles. Dogs lived out their life span with complete pathology conducted at the time of death. The radiation dose per cell turnover was characterized and related to the cause of death for each animal. Large doses per cell turnover resulted in acute death from lung damage with extensive cell killing, tissue disorganization, chronic inflammatory disease, fibrosis, and pneumonitis. Dogs with lower doses per cell turnover developed a very high frequency of lung cancer. As the dose per cell turnover was further decreased, no marked tissue damage and no significant change in either life span or lung cancer frequency was observed. Radiation induced tissue damage and chronic inflammatory disease results in high cancer frequencies in the lung. At doses where a high frequency of chromosome damage and mutations would be predicted to occur there was no decrease in life span or increase in lung cancer. Such research suggests that cell killing and tissue damage and the physiological responses to that damage are important mechanisms in radiation induced lung cancer.

The role of dose rate in radiation cancer risk: evaluating the effect of dose rate at the molecular, cellular and tissue levels using key events in critical pathways following exposure to low LET radiation.

PURPOSE: This review evaluates the role of dose rate on cell and molecular responses. It focuses on the influence of dose rate on key events in critical pathways in the development of cancer. This approach is similar to that used by the U.S. EPA and others to evaluate risk from chemicals. It provides a mechanistic method to account for the influence of the dose rate from low-LET radiation, especially in the low-dose region on cancer risk assessment. Molecular, cellular, and tissues changes are observed in many key events and change as a function of dose rate. The magnitude and direction of change can be used to help establish an appropriate dose rate effectiveness factor (DREF). CONCLUSIONS: Extensive data on key events suggest that exposure to low dose-rates are less effective in producing changes than high dose rates. Most of these data at the molecular and cellular level support a large (2-30) DREF. In addition, some evidence suggests that doses delivered at a low dose rate decrease damage to levels below that observed in the controls. However, there are some data human and mechanistic data that support a dose-rate effectiveness factor of 1. In summary, a review of the available molecular, cellular and tissue data indicates that not only is dose rate an important variable in understanding radiation risk but it also supports the selection of a DREF greater than one as currently recommended by ICRP ( 2007 ) and BEIR VII (NRC/NAS 2006 ).

Paradigm shifts in radiation biology: their impact on intervention for radiation-induced disease.

New mechanistic cell and molecular studies on the effects of very low doses of radiation have resulted in three major paradigm shifts. First, the observation of bystander effects demonstrated that non-hit cells may respond as well as cells in which energy is deposited. Second, it was thought that gene mutations and chromosome aberrations were the most important early changes that represented the initiation phase of radiation-induced cancer. Now genomic instability that leads to the loss of genetic control appears to play a major role in the development of cancer. Finally, recent studies have demonstrated that radiation-induced changes in gene expression can be demonstrated at very low radiation doses. These changes can result in alterations in response pathways, many of which appear to be involved in protective or adaptive responses. The demonstration that unique genes are up- and down-regulated depending on the radiation type, dose and dose rate suggests that different molecular mechanisms are involved in responses to high and low radiation doses. The ability to alter radiation response by physical and chemical treatments suggests that it may be possible to intervene in the progression of radiation-induced diseases. Such intervention may decrease the cancer risk from radiation exposure. This new research also demonstrates that many nonlinear biological processes have an impact on the induction of cancer and the shape of dose-response functions. Thus, for low-LET radiation delivered at low dose rates, the linear, no-threshold hypothesis is not well supported, but it is adequately conservative in protecting against low-dose radiation risks.

A Commentary on: "A History of the United States Department of Energy (DOE) Low Dose Radiation Research Program: 1998-2008".

This commentary provides a very brief overview of the book "A History of the United States Department of Energy (DOE) Low Dose Radiation Research Program: 1998-2008" ( http://lowdose.energy.gov ). The book summarizes and evaluates the research progress, publications and impact of the U.S. Department of Energy Low Dose Radiation Research Program over its first 10 years. The purpose of this book was to summarize the impact of the program's research on the current thinking and low-dose paradigms associated with the radiation biology field and to help stimulate research on the potential adverse and/or protective health effects of low doses of ionizing radiation. In addition, this book provides a summary of the data generated in the low dose program and a scientific background for anyone interested in conducting future research on the effects of low-dose or low-dose-rate radiation exposure. This book's exhaustive list of publications coupled with discussions of major observations should provide a significant resource for future research in the low-dose and dose-rate region. However, because of space limitations, only a limited number of critical references are mentioned. Finally, this history book provides a list of major advancements that were accomplished by the program in the field of radiation biology, and these bulleted highlights can be found in last part of chapters 4-10.

Evidence for 'bystander effects' in vivo.

The observation of bystander effects in vitro have raised some serious questions as to the appropriate target size for calculation radiation dose. This has implications on the risk from ionizing radiation since dose is often directly related to radiation risk. This paper demonstrates that bystander effects do occur in vivo. It demonstrates that at low dose rates the bystander effects and risk are limited to the organ where the radiation dose is delivered. On the other hand, exposure to high radiation dose rates produces clastogenic factors that are released into the blood. These factors have been demonstrated both in vitro and in vivo and may influence risk in organs not directly exposed to the radiation. Bystander effects suggest that organs respond as a unit and are not just a bag of individual cells acting independently. Dose and risk must consider this unit.

Changes in biomarkers from space radiation may reflect dose not risk.

This presentation evaluates differences between radiation biomarkers of dose and risk and demonstrates the consequential problems associated with using biomarkers to do risk calculations following radiation exposures to the complex radiation environment found in deep space. Dose is a physical quantity, while risk is a biological quantity. Dose does not predict risk. This manuscript discusses species sensitivity factors, tissue weighting factors, and radiation quality factors derived from relative biological effectiveness (RBE). These factors are used to modify dose to make it a better predictor of risk. At low doses, where it is not possible to measure changes in risk, biomarkers have been used incorrectly as an intermediate step in predicting risk. Examples of biomarkers that do not predict risk are reviewed. Species sensitivity factors were evaluated using the Syrian hamster and the Wistar rat. Although the frequency of chromosome damage is very similar in these two species, the Wistar rat is very sensitive to radiation-induced lung cancer while the Syrian hamster is very resistant. To illustrate problems involved in using tissue weighting factors, rat trachea and deep lung tissues were compared. The similar level of chromosome damage observed in these two tissues would predict that the risk for cancer induction would be the same. However, even though large numbers of deep lung tumors result from inhaled radon, under the same exposure conditions there has never been a tracheal tumor observed. Finally, the Relative Biological Effectiveness (RBE) used to generate "quality factors" that convert exposure and dose from different types of radiation to a single measure of risk, is discussed. Important risk comparisons are done at very low doses, where the response to the reference radiation has been shown to either increase or decrease as a function of dose. Thus, the RBE and the subsequent risk predicted is more dependent on the background response of the endpoint and the shape of the dose response to the reference radiation than it is on the radiation type of interest. A large study using micronuclei as biomarkers following exposure to different energies of mono-energetic neutrons, x-rays and gamma rays delivered at very low doses (0.0 to 0.10 Gy) is reported. As additional biomarkers of risk involved in critical steps in the carcinogenic process are developed, it may become possible to base risk estimates on biological change rather than the radiation energy deposition or dose.

Developing a scientific basis for radiation risk estimates: goal of the DOE Low Dose Research Program.

The U.S. Department of Energy's Low Dose Radiation Research Program is a 10 y activity currently funded at $21 million per year. It focuses on biological responses to low doses (<0.1 Gy) of low-LET ionizing radiation. The overall goal of this program is to provide a sound scientific basis for the radiation protection standards. The program supports basic research that combines modern genomic, molecular, and cellular techniques with recent advances in scientific instrumentation. These combinations make it possible to detect responses and test paradigms associated with the mechanisms of low dose radiation action not previously measurable or testable. Research to date is briefly reviewed and suggests the need for some major paradigm shifts. Exposure of the extracellular matrix can modify both the pattern of gene expression and the phenotype of the cells which result in cell transformation without direct mutation. Low dose radiation exposure results in a range of dose-response relationships for changes in the number, types, and patterns of gene expression. Such studies suggest an increased role for gene expression relative to single mutations for radiation induced cancer. Low dose research using microbeams demonstrated that cells do not require a direct "hit" to result in significant biological alterations. These "bystander effects" demonstrate that "non-hit" cells respond with changes in gene expression, DNA repair, chromosome aberrations, mutations, and cell killing. Research to link genomic instability with cancer is also being conducted and will be discussed. Detection of radiosensitivity genes as markers of genetic susceptibility in individuals and populations can be used in epidemiological studies to determine how molecular changes may impact risk. It is not possible to determine how this research will influence current radiation standards. However, the Low Dose Research Program will help ensure that radiation standards are set using the best scientific data available, and that they are adequate and appropriate for the protection of workers and the public.

Overview of low-level radiation exposure assessment: biodosimetry.

The capability to make diagnostic assessments of radiation exposure is needed to support triage of radiation casualties and medical treatment decisions in military operations. At the International Conference on Low-Level Radiation Injury and Medical Countermeasures session on biodosimetry in the military, participants reviewed the field of biomarkers, covering a wide range of biological endpoints. Participants evaluated early changes associated with exposure to ionizing radiation, including chromosomal and DNA damage, gene expression and associated proteins, and DNA mutations. The use and development of advanced monitoring and diagnostic technologies compatible with military operations was emphasized. Conventional radiation bioassays require a substantial amount of time between when the sample is taken and when the data can be provided for decision making. These "reach back" bioassays are evaluated in laboratories that are not in the field; these laboratories routinely measure exposures of 25 cGy (photon equivalent levels). Detection thresholds can be reduced approximately fivefold by the addition of significant and tiresome scoring efforts. Alternative real-time biomarkers that can be measured in field laboratories or with handheld detection devices show promise as screening and clinical diagnostic tools, but they require further development and validation studies.