Radiation hormesis
Encyclopedia
Radiation hormesis is the hypothesis
Hypothesis
A hypothesis is a proposed explanation for a phenomenon. The term derives from the Greek, ὑποτιθέναι – hypotithenai meaning "to put under" or "to suppose". For a hypothesis to be put forward as a scientific hypothesis, the scientific method requires that one can test it...

 that low doses of ionizing radiation
Ionizing radiation
Ionizing radiation is radiation composed of particles that individually have sufficient energy to remove an electron from an atom or molecule. This ionization produces free radicals, which are atoms or molecules containing unpaired electrons...

 (within the region and just above natural background levels
Background radiation
Background radiation is the ionizing radiation constantly present in the natural environment of the Earth, which is emitted by natural and artificial sources.-Overview:Both Natural and human-made background radiation varies by location....

) are beneficial, stimulating the activation of repair mechanisms that protect against disease
Disease
A disease is an abnormal condition affecting the body of an organism. It is often construed to be a medical condition associated with specific symptoms and signs. It may be caused by external factors, such as infectious disease, or it may be caused by internal dysfunctions, such as autoimmune...

, that are not activated in absence of ionizing radiation. The reserve repair mechanisms are hypothesized to be sufficiently effective when stimulated as to not only cancel the detrimental effects of ionizing radiation but also inhibit disease not related to radiation exposure (see hormesis
Hormesis
Hormesis is the term for generally favorable biological responses to low exposures to toxins and other stressors. A pollutant or toxin showing hormesis thus has the opposite effect in small doses as in large doses...

). This counter-intuitive hypothesis has captured the attention of scientists and public alike in recent years.

The Académie des Sciences — Académie nationale de Médecine (French Academy of Sciences
French Academy of Sciences
The French Academy of Sciences is a learned society, founded in 1666 by Louis XIV at the suggestion of Jean-Baptiste Colbert, to encourage and protect the spirit of French scientific research...

 — National Academy of Medicine) stated in their 2005 report concerning the effects of low-level radiation that many laboratory studies have observed radiation hormesis. However, they cautioned that it is not yet known if radiation hormesis occurs outside the laboratory, or in humans.

Consensus reports by the United States National Research Council
United States National Research Council
The National Research Council of the USA is the working arm of the United States National Academies, carrying out most of the studies done in their names.The National Academies include:* National Academy of Sciences...

 and the National Council on Radiation Protection and Measurements
National Council on Radiation Protection and Measurements
The National Council on Radiation Protection and Measurements is a U.S. organization. It has a congressional charter under Title 36 of the United States Code, but this does not imply it has any sort of oversight or supervision from Congress; it is not a government entity.This text appears on the...

 and the United Nations Scientific Committee on the Effects of Atomic Radiation
United Nations Scientific Committee on the Effects of Atomic Radiation
The United Nations Scientific Committee on the Effects of Atomic Radiation was set up by resolution of the United Nations General Assembly in 1955. 21 countries are designated to provide scientists to serve as members of the committee which holds formal meetings annually and submits a report to...

 (UNSCEAR) argue that there is no evidence for hormesis in humans and in the case of the National Research Council, that hormesis is outright rejected as a possibility. Therefore, the Linear no-threshold model
Linear no-threshold model
The linear no-threshold model is a method for predicting the long term, biological damage caused by ionizing radiation and is based on the assumption that the risk is directly proportional to the dose at all dose levels....

 (LNT) continues to be the model generally used by regulatory agencies for human radiation exposure.

Proposed mechanism and ongoing debate

Radiation hormesis proposes that radiation exposure comparable to and just above the natural background level of radiation
Background radiation
Background radiation is the ionizing radiation constantly present in the natural environment of the Earth, which is emitted by natural and artificial sources.-Overview:Both Natural and human-made background radiation varies by location....

 is not harmful but beneficial, while accepting that much higher levels of radiation are hazardous. Proponents of radiation hormesis typically claim that radio-protective responses in cells and the immune system not only counter the harmful effects of radiation but additionally act to inhibit spontaneous cancer not related to radiation exposure. Radiation hormesis stands in stark contrast to the more generally accepted linear no-threshold
Linear no-threshold model
The linear no-threshold model is a method for predicting the long term, biological damage caused by ionizing radiation and is based on the assumption that the risk is directly proportional to the dose at all dose levels....

 model (LNT), which states that the radiation dose-risk relationship is linear across all doses, so that small doses are still damaging, albeit less so than higher ones. Opinion pieces on chemical and radiobiological hormesis appeared in the journals Nature
Nature (journal)
Nature, first published on 4 November 1869, is ranked the world's most cited interdisciplinary scientific journal by the Science Edition of the 2010 Journal Citation Reports...

 and Science
Science (journal)
Science is the academic journal of the American Association for the Advancement of Science and is one of the world's top scientific journals....

 in 2003.

Assessing the risk of radiation at low doses (<100 mSv
Sievert
The sievert is the International System of Units SI derived unit of dose equivalent radiation. It attempts to quantitatively evaluate the biological effects of ionizing radiation as opposed to just the absorbed dose of radiation energy, which is measured in gray...

) and low dose rates (<1 mSv
Sievert
The sievert is the International System of Units SI derived unit of dose equivalent radiation. It attempts to quantitatively evaluate the biological effects of ionizing radiation as opposed to just the absorbed dose of radiation energy, which is measured in gray...

.min−1) is highly problematic and controversial. While epidemiological studies on populations of people exposed to an acute dose of high level radiation such as Japanese Atomic Bomb Survivors
Hibakusha
The surviving victims of the atomic bombings of Hiroshima and Nagasaki are called , a Japanese word that literally translates to "explosion-affected people"...

  have robustly upheld the LNT
Linear no-threshold model
The linear no-threshold model is a method for predicting the long term, biological damage caused by ionizing radiation and is based on the assumption that the risk is directly proportional to the dose at all dose levels....

, studies involving low doses and low dose rates have failed to detect any increased cancer rate. This is because the baseline cancer rate is already very high (causing 13% of all deaths in 2008) and it fluctuates wildly because of life style choices and viral disease, obscuring the subtle effects of low level radiation (an acute dose of 100 mSv
Sievert
The sievert is the International System of Units SI derived unit of dose equivalent radiation. It attempts to quantitatively evaluate the biological effects of ionizing radiation as opposed to just the absorbed dose of radiation energy, which is measured in gray...

 may cause a ~0.8% increase in cancer risk). In particular, variations in smoking prevalence or even patterns in reporting smoking cause wide variation in excess cancer and measurement error bias. Thus, even a large study of many thousands of subjects with imperfect smoking prevalence information will fail to detect the effects of low level radiation than a smaller study that properly compensates for smoking prevalence. Given the absence of direct epidemiological evidence, there is considerable debate as to whether the dose-response relationship in the low dose regime is supralinear, linear (LNT), has a threshold or sub-linear i.e. a hormetic response.

While most major consensus reports and government bodies currently adhere to LNT, the 2005 French Academy of Sciences
French Academy of Sciences
The French Academy of Sciences is a learned society, founded in 1666 by Louis XIV at the suggestion of Jean-Baptiste Colbert, to encourage and protect the spirit of French scientific research...

-National Academy of Medicine
Académie Nationale de Médecine
Académie Nationale de Médecine, or National Academy of Medicine was created in 1820 by king Louis XVIII at the urging of baron Antoine Portal. At its inception, the institution was known as the Académie Royale de Médecine...

's report concerning the effects of low-level radiation rejected LNT as a scientific model of carcinogenic risk for doses below 100 mSv
Sievert
The sievert is the International System of Units SI derived unit of dose equivalent radiation. It attempts to quantitatively evaluate the biological effects of ionizing radiation as opposed to just the absorbed dose of radiation energy, which is measured in gray...

. They consider there to be several dose-effect relationships rather than only one, and that these relationships have many variables such as target tissue, radiation dose, dose rate and individual sensitivity factors. They request that further study is required on low doses (less than 100 mSv
Sievert
The sievert is the International System of Units SI derived unit of dose equivalent radiation. It attempts to quantitatively evaluate the biological effects of ionizing radiation as opposed to just the absorbed dose of radiation energy, which is measured in gray...

) and very low doses (less than 10 mSv
Sievert
The sievert is the International System of Units SI derived unit of dose equivalent radiation. It attempts to quantitatively evaluate the biological effects of ionizing radiation as opposed to just the absorbed dose of radiation energy, which is measured in gray...

) as well as the impact of tissue type and age. The Academy considers the LNT model is only useful for regulatory purposes as it simplifies the administrative task. They furthermore point out that approximately 40% of laboratory studies on cell cultures and animals report some degree of radiobiological hormesis, they state:

"...its existence in the laboratory is beyond question and its mechanism of action appears well understood."


They go on to outline a growing body of research that illustrates that the human body is not a passive accumulator of radiation
Ionizing radiation
Ionizing radiation is radiation composed of particles that individually have sufficient energy to remove an electron from an atom or molecule. This ionization produces free radicals, which are atoms or molecules containing unpaired electrons...

 damage but it actively repairs the damage caused via a number of different processes, including:
  • Mechanisms that mitigate reactive oxygen species generated by ionizing radiation and oxidative stress
    Oxidative stress
    Oxidative stress represents an imbalance between the production and manifestation of reactive oxygen species and a biological system's ability to readily detoxify the reactive intermediates or to repair the resulting damage...

    .
  • Apoptosis
    Apoptosis
    Apoptosis is the process of programmed cell death that may occur in multicellular organisms. Biochemical events lead to characteristic cell changes and death. These changes include blebbing, cell shrinkage, nuclear fragmentation, chromatin condensation, and chromosomal DNA fragmentation...

     of radiation damaged cells that may undergo tumorigenesis is initiated at only few mSv.
  • Cell death during meiosis
    Meiosis
    Meiosis is a special type of cell division necessary for sexual reproduction. The cells produced by meiosis are gametes or spores. The animals' gametes are called sperm and egg cells....

     of radiation damaged cells that were unsuccessfully repaired.
  • The existence of a cellular signaling system that alerts neighboring cells of cellular damage.
  • The activation of enzymatic
    Enzyme
    Enzymes are proteins that catalyze chemical reactions. In enzymatic reactions, the molecules at the beginning of the process, called substrates, are converted into different molecules, called products. Almost all chemical reactions in a biological cell need enzymes in order to occur at rates...

     DNA repair
    DNA repair
    DNA repair refers to a collection of processes by which a cell identifies and corrects damage to the DNA molecules that encode its genome. In human cells, both normal metabolic activities and environmental factors such as UV light and radiation can cause DNA damage, resulting in as many as 1...

     mechanisms around 10 mSv.
  • Modern DNA microarray
    DNA microarray
    A DNA microarray is a collection of microscopic DNA spots attached to a solid surface. Scientists use DNA microarrays to measure the expression levels of large numbers of genes simultaneously or to genotype multiple regions of a genome...

     studies which show that numerous genes
    Gênes
    Gênes is the name of a département of the First French Empire in present Italy, named after the city of Genoa. It was formed in 1805, when Napoleon Bonaparte occupied the Republic of Genoa. Its capital was Genoa, and it was divided in the arrondissements of Genoa, Bobbio, Novi Ligure, Tortona and...

     are activated at radiation
    Ionizing radiation
    Ionizing radiation is radiation composed of particles that individually have sufficient energy to remove an electron from an atom or molecule. This ionization produces free radicals, which are atoms or molecules containing unpaired electrons...

     doses well below the level that mutagenesis
    Mutagenesis
    Mutagenesis is a process by which the genetic information of an organism is changed in a stable manner, resulting in a mutation. It may occur spontaneously in nature, or as a result of exposure to mutagens. It can also be achieved experimentally using laboratory procedures...

     is detected.
  • Radiation
    Ionizing radiation
    Ionizing radiation is radiation composed of particles that individually have sufficient energy to remove an electron from an atom or molecule. This ionization produces free radicals, which are atoms or molecules containing unpaired electrons...

    -induced tumorigenesis may have a threshold related to damage density, as revealed by experiments that employ blocking grids to thinly distribute radiation
    Ionizing radiation
    Ionizing radiation is radiation composed of particles that individually have sufficient energy to remove an electron from an atom or molecule. This ionization produces free radicals, which are atoms or molecules containing unpaired electrons...

    .
  • A large increase in tumours in immunosuppressed individuals illustrates that the immune system efficiently destroys aberrant cells and nascent tumors.
  • Increased sensitivity to radiation induced cancer in the inherited condition Ataxia-telangiectasia like disorder, illustrates the damaging effects of loss of the repair gene Mre11h resulting in the inability to fix DNA double-strand breaks.


However, as the BEIR-VII report points out, "the presence of a true dose threshold demands totally error-free DNA damage response and repair." The specific damage they worry about is double strand breaks (DSBs) and they continue, "error-prone nonhomologous end joining (NHEJ) repair in postirradiation cellular response, argues strongly against a DNA repair-mediated low-dose threshold for cancer initiation".

Radon gas in homes is the largest source of radiation dose for most individuals and it is generally advised that the concentration be kept below 150 Bq/m³ (4 pCi/L). A recent retrospective case-control study of lung cancer risk showed substantial cancer rate reduction between 50 and 123 Bq per cubic meter relative to a group at zero to 25 Bq per cubic meter. This study is cited as evidence for hormesis, but a single study all by itself cannot be regarded as definitive. Other studies into the effects of domestic radon
Radon
Radon is a chemical element with symbol Rn and atomic number 86. It is a radioactive, colorless, odorless, tasteless noble gas, occurring naturally as the decay product of uranium or thorium. Its most stable isotope, 222Rn, has a half-life of 3.8 days...

 exposure have not reported a hormetic effect; including for example the respected "Iowa Radon Lung Cancer Study" of Field et al. (2000), which also used sophisticated radon exposure dosimetry
Dosimetry
Radiation dosimetry is the measurement and calculation of the absorbed dose in matter and tissue resulting from the exposure to indirect and direct ionizing radiation...

. In addition, Darby et al. (2005) argue that radon exposure is negatively correlated with the tendency to smoke and environmental studies need to accurately control for this; people living in urban areas where smoking rates are higher usually have lower levels of radon exposure due the increased prevalence of multi-story dwellings. When doing so, they found a significant increase in lung cancer amongst smokers exposed to radon at doses as low as 100 to 199 Bq m−3 and warned that smoking greatly increases the risk posed by radon exposure i.e. reducing the prevalence of smoking would decrease deaths caused by radon.

Furthermore, particle microbeam studies show that passage of even a single alpha particle (e.g. from radon and its progeny) through cell nuclei is highly mutagenic, and that alpha radiation may have a higher mutagenic effect at low doses (even if a small fraction of cells are hit by alpha particles) than predicted by linear no-threshold model, a phenomena attributed to bystander effect
Bystander effect (radiobiology)
The Radiation-Induced Bystander Effect is the phenomenon in which unirradiated cells exhibit irradiated effects as a result of signals received from nearby irradiated cells....

. However, there is currently insufficient evidence at hand to suggest that the bystander effect promotes carcinogenesis
Carcinogenesis
Carcinogenesis or oncogenesis is literally the creation of cancer. It is a process by which normal cells are transformed into cancer cells...

 at low doses.

Given the uncertain effects of low-level radiation, there is a pressing need for good quality research in this area. An expert panel convened at the 2006 Ultra-Low-Level Radiation Effects Summit at Carlsbad, New Mexico, proposed the construction of an Ultra-Low-Level Radiation laboratory
Laboratory
A laboratory is a facility that provides controlled conditions in which scientific research, experiments, and measurement may be performed. The title of laboratory is also used for certain other facilities where the processes or equipment used are similar to those in scientific laboratories...

. The laboratory, if built, will investigate the effects of almost no radiation on laboratory animals and cell culture
Cell culture
Cell culture is the complex process by which cells are grown under controlled conditions. In practice, the term "cell culture" has come to refer to the culturing of cells derived from singlecellular eukaryotes, especially animal cells. However, there are also cultures of plants, fungi and microbes,...

s, and it will compare these groups to control groups exposed to natural radiation levels. The expert panel believes that the Ultra-Low-Level Radiation laboratory is the only experiment
Experiment
An experiment is a methodical procedure carried out with the goal of verifying, falsifying, or establishing the validity of a hypothesis. Experiments vary greatly in their goal and scale, but always rely on repeatable procedure and logical analysis of the results...

 that can explore with authority and confidence the effects of low-level radiation; that it can confirm or discard the various radiobiological effects proposed at low radiation levels e.g. LNT
Linear no-threshold model
The linear no-threshold model is a method for predicting the long term, biological damage caused by ionizing radiation and is based on the assumption that the risk is directly proportional to the dose at all dose levels....

, threshold and radiation hormesis.

Statements by leading nuclear bodies

Radiation hormesis has not been accepted by either the United States National Research Council
United States National Research Council
The National Research Council of the USA is the working arm of the United States National Academies, carrying out most of the studies done in their names.The National Academies include:* National Academy of Sciences...

, or the National Council on Radiation Protection and Measurements
National Council on Radiation Protection and Measurements
The National Council on Radiation Protection and Measurements is a U.S. organization. It has a congressional charter under Title 36 of the United States Code, but this does not imply it has any sort of oversight or supervision from Congress; it is not a government entity.This text appears on the...

. In addition, the United Nations Scientific Committee on the Effects of Atomic Radiation
United Nations Scientific Committee on the Effects of Atomic Radiation
The United Nations Scientific Committee on the Effects of Atomic Radiation was set up by resolution of the United Nations General Assembly in 1955. 21 countries are designated to provide scientists to serve as members of the committee which holds formal meetings annually and submits a report to...

 (UNSCEAR) wrote in its most recent report:
Until the [...] uncertainties on low-dose response are resolved, the Committee believes that an increase in the risk
of tumour induction proportionate to the radiation dose is consistent with developing knowledge and that it remains, accordingly, the most scientifically defensible approximation of low-dose response. However, a strictly linear dose response should not be expected in all circumstances.


This is a reference to the fact that very low doses of radiation have only marginal impacts on individual health outcomes. It is therefore difficult to detect the 'signal' of decreased or increased morbidity and mortality due to low-level radiation exposure in the 'noise' of other effects. The notion of radiation hormesis has been rejected by the National Research Council's (part of the National Academy of Sciences) 16 year long study on the Biological Effects of Ionizing Radiation. "The scientific research base shows that there is no threshold of exposure below which low levels of ionizing radiation can be demonstrated to be harmless or beneficial. The health risks – particularly the development of solid cancers in organs – rise proportionally with exposure" says Richard R. Monson, associate dean for professional education and professor of epidemiology, Harvard School of Public Health, Boston.

The possibility that low doses of radiation may have beneficial effects (a phenomenon often referred to as “hormesis”) has been the subject of considerable debate. Evidence for hormetic effects was reviewed, with emphasis on material published since the 1990 BEIR V study on the health effects of exposure to low levels of ionizing radiation. Although examples of apparent stimulatory or protective effects can be found in cellular and animal biology, the preponderance of available experimental information does not support the contention that low levels of ionizing radiation have a beneficial effect. The mechanism of any such possible effect remains obscure. At this time, the assumption that any stimulatory hormetic effects from low doses of ionizing radiation will have a significant health benefit to humans that exceeds potential detrimental effects from radiation exposure at the same dose is unwarranted.

Cultures

Studies in cell cultures can be useful for finding mechanisms for biological processes, but they can be criticized for not effectively capturing the whole of the living organism.

A study by E.I. Azzam suggested that pre-exposure to radiation causes cells to turn on protection mechanisms. A different study by de Toledo and collaborators, has shown that irradiation with gamma rays increases the concentration of glutathione, an antioxidant found in cells.

Animals

A study by Otsuka and collaborators find hormesis in whole animals. Miyachi conducted a study on mice and found that a 200 mGy X-ray dose protects mice against both further X-ray exposure and ozone gas. In another rodent study, Sakai and collaborators found that (1 mGy/hr) gamma irradiation prevents the development of cancer (induced by chemical means, injection of methylcholanthrene
Methylcholanthrene
Methylcholanthrene is a highly carcinogenic polycyclic aromatic hydrocarbon produced by burning organic compounds at very high temperatures. It is a yellow solid with a melting point around 180 °C. Methylcholanthrene is used in laboratory studies of chemical carcinogenesis. It is an...

).

In a 2006 paper, a dose of 1 Gy was delivered to the cells (at constant rate from a radioactive source) over a series of lengths of time. These were between 8.77 and 87.7 hours, the abstract states for a dose delivered over 35 hours or more (low dose rate) no transformation of the cells occurred. Also for the 1 Gy dose delivered over 8.77 to 18.3 hours that the biological effect (neoplastic transformation) was about 1.5 times smaller than that which that had been observed using a single high dose rate of X-ray photons of similar energy. Likewise it has been reported that fractionation of gamma irradiation reduces the likelihood of a neoplastic transformation. Pre-exposure to fast neutrons and gamma rays from Cs-137 is reported to increase the ability of a second dose to induce a neoplastic transformation.

However, caution must be used in interpreting these results, as it noted in the BEIR VII report, these pre-doses can also increase cancer risk:

In chronic low-dose experiments with dogs (75 mGy/d for the duration of life), vital hematopoietic progenitors showed increased radioresistance along with renewed proliferative capacity (Seed and Kaspar 1992). Under the same conditions, a subset of animals showed an increased repair capacity as judged by the unscheduled DNA synthesis assay (Seed and Meyers 1993). Although one might interpret these observations as an adaptive effect at the cellular level, the exposed animal population experienced a high incidence of myeloid leukemia and related myeloproliferative disorders. The authors concluded that “the acquisition of radioresistance and associated repair functions under the strong selective and mutagenic pressure of chronic radiation is tied temporally and causally to leukemogenic transformation by the radiation exposure” (Seed and Kaspar 1992).

2004 Taiwan cobalt-contaminated steel

In popular treatments of radiation hormesis, a study of the inhabitants of apartment buildings in Taiwan has received prominent attention. The building materials had been accidentally contaminated with Cobalt-60 but the study found cancer mortality rates more than 20 times lower than in the population as a whole. However, this study compared the relatively young irradiated population with the much older general population of Taiwan, which is a major flaw. A subsequent study by Hwang et al. (2006) found a significant exposure-dependent increase in cancer in the irradiated population, particularly leukemia in men and thyroid cancer in women, though this trend is only detected amongst those who were first exposed before the age of 30. This study also found that rate of total cancer cases was lower than expected.

See also

  • Hormesis
    Hormesis
    Hormesis is the term for generally favorable biological responses to low exposures to toxins and other stressors. A pollutant or toxin showing hormesis thus has the opposite effect in small doses as in large doses...

  • Dose fractionation
    Dose fractionation
    Experiments in radiation biology have found that as the absorbed dose of radiation increases, the number of cells which survive decreases. They have also found that if the radiation is fractionated into smaller doses, with one or more rest periods in between, fewer cells die. This is because of...

  • Linear no-threshold model
    Linear no-threshold model
    The linear no-threshold model is a method for predicting the long term, biological damage caused by ionizing radiation and is based on the assumption that the risk is directly proportional to the dose at all dose levels....

  • Petkau effect
    Petkau effect
    The Petkau effect is an early counterexample to linear-effect assumptions usually made about radiation exposure. It was found by Dr. Abram Petkau at the Atomic Energy of Canada Whiteshell Nuclear Research Establishment, Manitoba and published in Health Physics March 1972.Petkau had been...

  • Radioresistance
    Radioresistance
    Radioresistance is the property of organisms that are capable of living in environments with very high levels of ionizing radiation.Radioresistance is surprisingly high in many organisms, in contrast to previously held views...

  • Background radiation
    Background radiation
    Background radiation is the ionizing radiation constantly present in the natural environment of the Earth, which is emitted by natural and artificial sources.-Overview:Both Natural and human-made background radiation varies by location....

  • Ramsar, Mazandaran

External links

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