Research on Health Effects of Low-Level Ionizing Radiation Exposure Opportunities for the Armed Forces Radiobiology Research Institute (2014) / Chapter Skim
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2 Current Directions in Radiobiological Research
2 Current Directions in Radiobiological Research
Pages 27-52
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From page 27... ...
The focus is on research findings released after publication of two comprehensive re views on the effects of low-level ionizing radiation: the National Research Council's Health Risks from Exposure to Low Levels of Ionizing Radiation (known as the Biological Effects of Ionizing Radiation VII or the "BEIR VII" report (NRC, 2006) and the United Nations Scientific Committee on the Effects of Atomic Radiation's (UNSCEAR's)
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Low-dose radiation research involves observational studies of popu lations and experimental studies of radiation effects on molecules, cells, tissues, and animal models. Epidemiological studies provide information about possible associations between exposure to low-dose radiation and disease in humans.
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Department of Energy (DOE) Low Dose Radiation Research Program began work in 1999 to investigate radia tion effects on genomes and cells to better understand outcomes in living organisms and develop radiation protection standards based on risk.
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and low dose rates, radiation-protection standards and exposure limits that require an assessment of risks are set by assuming that there is a linear relationship between exposure and effect and by extrapolating from the outcomes observed at higher radiation levels. This is called the linear no-threshold (LNT)
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Copyright 2003, with permission from the National Academy of Sciences, U.S.A. research to characterize the health risks at low radiation doses with more certainty.
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Figure 2-2 illus trates RBE as a function of surviving fraction.5 The primary difference between the high- and low-LET radiation dose-response curves is the reduc tion of the curve's so-called shoulder region with increasing LET. In the low-dose region of low-LET radiation, damage is due primarily to single tracks' acting independently, and it is relatively easier for cells to repair this form of damage.
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For cell killing, the RBE is easily quantified at high doses; differences in effects at low doses are more difficult to determine with confidence. In addition, the frequency of events in most cells is zero at low mean doses of high-LET radiation, with a few cells having only one event and the rare cell having more than one event.
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Indeed, for exposure to radon and its progeny (through alpha particles) , evidence exists that radiation-induced cancer risks actually increase at low dose rates (Lubin et al., 1995; NRC, 1999)
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. Using Radiation Biology to Augment Radiation Epidemiological Studies Although experimental radiation biology cannot currently provide d irect models for estimating low-dose radiation health risks in humans, there is much interest in using radiobiology to augment epidemiological studies (Preston et al., 2013)
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However, thus far only rather rare mutations have been shown to have an appreciably heightened radiation effect. Given the role of BRCA1 and BRCA2 genes in the repair of DNA double-strand breaks and the high prevalence of breast cancer among women carriers, for example, investigators have hypothesized and observed that mutations in these genes enhance the radiation-associated increase in breast cancer after exposure to ionizing radiation from diagnostic X-rays (Andrieu et al., 2006)
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. Although much is known about the DNA damage induced by the deposiion of energy from exposure to ionizing radiation and the subse t quent cellular responses, a significant gap exists in the understanding of how these might lead to detrimental health effects years after exposure.
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Invasive; not useful for partial-body exposures Neutron activation 0.0001 Neutron specific Not for partial-body exposures SOURCE: Adapted from Ainsbury et al., 2011. Review of retrospective dosimetry techniques for external ionising radiation exposures.
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. However, currently there is no scientific knowledge as to whether or how these phenomena and processes would deviate cancer risks at very low doses from those predicted by linear extrapolation from low doses (Brenner et al., 2003)
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Epidemiological Study Designs Cohort Studies Cohort studies typically follow a group of exposed and a group of un exposed individuals over time to determine disease occurrence in relation to radiation exposure. Much of what we know about cancer risks at lower radiation levels comes from the study of the atomic-bombing survivors of 8 Bias is an error in the measurement of a factor that can arise, for example, from choos ing study subjects that are not representative of the overall population (i.e., selection bias)
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Proximity to the hypocenter in Hiroshima, for example, was not only related to radiation exposure from the bomb but also potentially related to each individual's occupation, socioeconomic status (SES) , and other independent risk factors for mortality that simultaneously can be correlated with dose.
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, a highly influential case-control study on low-dose ionizing radiation effects (Doll and Wakeford, 1997; NCRP, 2013)
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populations published in the BEIR VII report (NRC, 2006) and the increasing acceptance of the limitations of epidemiological studies of low-dose radiation exposures (Berrington et al., 2011)
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questioned whether the relationship is causal. The same logic -- focusing on subgroups of the population in which the excessive relative risk of cancer after radiation exposure is posited to be largest -- applies to two more recently published epidemiological studies of cancer risks associated with pediatric exposure to computed tomogra phy (CT)
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Other Health Consequences Radiation exposure at doses higher than 1 Gy is associated with many noncancer health effects, but little existing evidence addresses such effects at doses less than 1 Gy. Many questions remain about biological mecha nisms operating at moderately high to low (i.e., at the 100 mGy–1 Gy range)
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From page 46... ...
Although much is known about the health effects after exposure to radiaion at the 100 mGy–1 Gy dose range and high dose rates, the scien t tific uncertainty concerning the effects of low-dose radiation is considerable. Debate continues about how to extrapolate radiation risks at low doses, the biological effectiveness of low-dose radiation, and the effects of dose rate and external versus internal exposure.
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From page 47... ...
There are thus a number of unanswered questions concerning the h uman health effects of low-dose ionizing radiation exposures and, al though scientific advances provide opportunities to address them, there are also significant challenges associated with moving forward. Chapter 5 discusses opportunities for AFRRI to contribute to the body of knowledge on the health effects of low-dose ionizing radiation in ways relevant to its mission and offers recommendations on possible courses of action.
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2003. Cancer risks attributable to low doses of ionizing radiation: Assessing what we really know.
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2009. High Level and Expert Group report -- European low dose risk research radiation protection.
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2003. Is there a common mechanism underlying genomic instability, bystander effects and other nontargeted effects of exposure to ionizing radiation?
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2006. Health risks from exposure to low levels of ionizing radiation: BEIR VII: Phase 2.
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2010. Radiation exposure and circulatory disease risk: Hiroshima and Nagasaki atomic bomb survivor data, 1950-2003.
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