Radiation Hormesis - Proposed Mechanism and Ongoing Debate

Proposed Mechanism and Ongoing Debate

Radiation hormesis proposes that radiation exposure comparable to and just above the natural background level of radiation 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 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 and Science in 2003.

Assessing the risk of radiation at low doses (<100 mSv) and low dose rates (<0.1 mSv.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 (被爆者?)) have robustly upheld the LNT (mean dose ~210 mSv), 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 (~42 of 100 people will be diagnosed in their lifetime) and it fluctuates ~40% because of lifestyle and environmental effects, obscuring the subtle effects of low level radiation. Epidemiological studies maybe capable of detecting elevated cancer rates as low as 1.2 to 1.3 i.e. 20% to 30% increase. But for low doses (1–100 mSv) the predicted elevated risks are only 1.001 to 1.04 and excess cancer cases, if present, cannot be detected due to confounding factors, errors and biases.

In particular, variations in smoking prevalence or even accuracy 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 <100 mSv 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-National Academy of Medicine's report concerning the effects of low-level radiation rejected LNT as a scientific model of carcinogenic risk at low doses.

"Using LNT to estimate the carcinogenic effect at doses of less than 20 mSv is not justified in the light of current radiobiologic knowledge."

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) and very low doses (less than 10 mSv) 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. Quoting results from literature research, they furthermore claim that approximately 40% of laboratory studies on cell cultures and animals indicate some degree of chemical or radiobiological hormesis, and 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 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.
• 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.

Furthermore, 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.

The BEIR-VII report argued that, "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". Resent research observed that DSBs caused by CAT scans are repaired within 24-hours and DSBs maybe more efficiently repaired at low doses, suggesting the risk ionizing radiation at low doses may not by directly proportional to the dose. However, it is not known if low dose ionizing radiation stimulates the repair of DSBs not caused by ionizing radiation i.e. a hormetic response.

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 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. 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 phenomenon attributed to bystander effect. However, there is currently insufficient evidence at hand to suggest that the bystander effect promotes carcinogenesis in humans at low doses.