Radiation hormesis

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Radiation hormesis (also called radiation homeostasis) is the hypothesis that chronic low doses of ionizing radiation are beneficial, stimulating repair mechanisms that protect against disease.^[1][2][3][4] The Académie des Sciences — Académie nationale de Médecine (French Academy of Sciences — National Academy of Medicine) stated in their 2005 report concerning the effects of low-level radiation that many laboratory studies have observed radiation hormesis.^[5][6] However, they cautioned that it is not yet known if radiation hormesis occurs outside the laboratory, in humans.^[7]

Consensus reports by the United States National Research Council and the National Council on Radiation Protection and Measurements and the United Nations Scientific Committee on the Effects of Atomic Radiation (UNSCEAR) have upheld that insufficient human data on radiation hormesis exists to supplant the Linear no-threshold model (LNT). Therefore, the LNT continues to be model generally used by regulatory agencies for human radiation exposure.

Contents 1 Proposed mechanism and ongoing debate 2 Statements by leading nuclear bodies 3 Studies of Low Level Radiation 3.1 Studies in cultures 3.2 Studies in animals 3.3 Taiwan Study 4 See also 5 External links 6 References

[edit] Proposed mechanism and ongoing debate

Proponents of radiation hormesis accept that high radiation levels are harmful; that intense artificial radiation, for example, is toxic. But they believe that low levels of radiation, comparable to the natural background level of radiation are not harmful. The subject of radiation hormesis has captured the attention of scientists and public alike in recent years, perhaps because of its counter-intuitive properties. Opinion pieces on chemical and radiobiological hormesis appeared in the journals Nature^[1] and Science^[3] in 2003.

While most major studies have used the linear no-threshold model (LNT),^[8] the 2005 French Academy of Sciences-National Academy of Medicine's report concerning the effects of low-level radiation rejects LNT as a scientific model of carcinogenic risk associated for doses less than 100mSv. 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 propose that more study is done on low doses (less than 100mSv) and very low doses (less than 10mSv)as well as the impact of tissue type and age. Low to moderate levels of radiation poses no risk to human health below a threshold comparable to natural radiation. The Academy considers the LNT model useful for regulatory purposes as it simplifies the administrative task. However, they also point out that approximately 40% of laboratory studies on cell cultures and animals report some sort of radiobiological hormesis.^[7] They state:

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

They go on to outline the growing body of research that illustrates that the human body is not a passive accumulator of radiation damage but it actively repairs the damage caused via a number of different processes, including:^[7]

• Mechanisms that mitigate reactive oxygen species generated by ionising radiation and oxidative stress.
• Apoptosis of radiation damaged cells that may undergo tumorigenesis is initiated at only few mSv.
• Cell death during meiosis 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 DNA repair mechanisms around 10 mSv.
• Modern DNA microarray studies which show that numerous genes are activated at radiation doses well below the level that mutagenesis is detected.
• Radiation induced tumorigenesis may have a threshold related to damage density, as revealed by experiments that employ blocking grids to thinly distribute radiation.
• A large increase in tumours in immunosuppressed individuals illustrates that the immune system efficiently destroys aberrant cells and nascent tumors.

Most epidemiological studies on populations of people have upheld LNT without noting a contradiction, these studies reject radiation hormesis. Epidemiological studies at the lowest levels of radiation are very difficult to interpret because of confounding factors. For example, smoking rates (or even patterns in reporting smoking) cause huge problems in estimating excess cancer rates in observational studies. In addition, measurement error biases estimates towards zero so that a study of a hundred of thousand can be less powerful at identifying an effect of radiation hormesis than one of under a thousand.^[9]

Radon gas in homes is the largest source of radiation dose for most individuals and it is generally advised that the dose be kept below 150 Bq/m^3 (4 pCi/L).^[10] 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.^[11] 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 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.^[12] In addition, Darby et al. argue that radon exposure is negatively correlated with the tenancy to smoke, so environmental studies need to accurately control for this. When doing so they found a significant increase in lung cancer for those with doses as low as 100 to 199 Bq m^-3.^[13]

Given the uncertain effects of low-level radiation, there is a pressing need for good quality research in this area.^[14] 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.^[14] The laboratory, if built, will investigate the effects of almost no radiation on laboratory animals and cell cultures, and it will compare these groups to control groups exposed to natural radiation levels.^[14] The expert panel believes that the Ultra-Low-Level Radiation laboratory is the only experiment 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, threshold and radiation hormesis.

[edit] Statements by leading nuclear bodies

Radiation hormesis has not been accepted by both the United States National Research Council^[15] and the National Council on Radiation Protection and Measurements.^[16] In addition, the United Nations Scientific Committee on the Effects of Atomic Radiation (UNSCEAR) wrote in its most recent report:^[17]

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 [3]. See the National Academies Press book Health Risks from Exposure to Low Levels of Ionizing Radiation: BEIR VII Phase 2.

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 [4].

[edit] Studies of Low Level Radiation

Over the years, many studies have been carried out on the effects of low level radiation. Despite that, there are no agreed answers. Studies which conflict with the dominant view (LNT) are more notable and could be more likely to be published or alternately could be less likely to be published since publication bias normally means that results which contradict the dominant paradgim are the ones that don't get published.

[edit] Studies in cultures

A study by E.I. Azzam suggested that pre-exposure to radiation causes cells to turn on protection mechanisms, ^[18] 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.^[19]

[edit] Studies in animals

A study by Otsuka and collaborators find hormesis in whole animals ^[20]. 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.^[21] In another rodent study, Sakai and collaborators found that (1 mGy hr-1) gamma irradiation prevents the development of cancer (induced by chemical means, injection of methylcholanthrene).^[22]

In a 2006 paper^[23] 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 ^[24]. 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.^[25]

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) [5].

[edit] Taiwan Study

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 rates 96.4% lower than in the population as a whole.^[26].

However, this study has been considered to have next to no scientific value, because it compares the irradiated population with the much older general population of Taiwan. 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.^[27]

[edit] See also

• Hormesis
• Dose fractionation
• Electromagnetic therapy
• Linear no-threshold model
• Petkau effect
• Radioresistance

[edit] External links

• Health Risks from Exposure to Low Levels of Ionizing Radiation: BEIR VII Phase 2
• Radiation Hormesis Overview by T. D. Luckey, who wrote a book on the subject (Luckey, T. D. (1991). Radiation Hormesis. Boca Raton, FL: CRC Press. ISBN 0-8493-6159-1)
• Cancer risks attributable to low doses of ionizing radiation: Assessing what we really know, Proceedings of the National Academy of Sciences of the USA.

[edit] References