Extrapolating radiation-induced cancer risks from low doses to very low doses

Center for Radiological Research, Columbia University Medical Center, 630 West 168th Street, New York, NY 10032, USA.
Health physics (Impact Factor: 1.27). 11/2009; 97(5):505-9. DOI: 10.1097/HP.0b013e3181ad7f04
Source: PubMed


There is strong evidence that ionizing radiation increases cancer risks at high doses (e.g., >or=1 Gy), and persuasive, if controversial, epidemiological evidence that cancer risks are increased at low doses ( approximately 10 mGy). Discussed here are the issues related to extrapolating radiation risks from low radiation doses to very low doses (<or=1 mGy) - for which purpose we are forced to rely on radiobiological evidence and biophysical arguments. At high doses, cells are typically hit by many tracks of radiation, while at low doses most cells are typically hit by a single track of radiation; at very low doses proportionately fewer cells are hit, again only by a single track of radiation. Thus, in comparing low doses to very low doses, the damage to hit cells remains essentially the same (a single radiation track passing through a cell), but what changes is the number of cells that are subjected to this same damage, which decreases linearly as the dose decreases. This is the argument for a linear no-threshold (LNT) model. It is important to emphasize that this LNT argument only applies to the extrapolation from low doses to very low doses, not from high to low doses. Of course there are caveats to this argument, such as the potential effects of phenomena such as inter-cellular communication and immunosurveillance, and the possibility of different radiobiological processes at very low doses, compared to low doses. However, there is little conclusive experimental evidence about the significance of these phenomena at very low doses, and comparative mechanistic studies at high doses vs. low doses will not be informative in this context. At present, we do not know whether such radiobiological phenomena would produce small or large perturbations, or even whether they would increase or decrease cancer risks at very low doses, compared with the prediction of a linear extrapolation from low doses.

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    • "However, it remains very diffi cult to assess the potential of small radiation-induced changes in cancer risk in the low-dose range. For the extrapolation of radiation risks to very low doses ( Յ 1 mGy) and to substantiate the epidemiological evidence for radiation eff ects at low doses of the order of 10 mGy, we are forced to rely on radiobiological evidence and biophysical arguments (Brenner 2009, Pernot et al. 2012). IR can induce a variety of DNA damage either directly or indirectly through ionization events produced by radiation-induced reactive oxygen species (ROS). "
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    • "The errors in the cancer risk model as presented in the BEIR VII report are estimated at a factor of 2 or 3 for the purpose of estimating risks from low-dose x-ray exposure (National Research Council 2006). In addition, carcinogenic risks induced by low doses and also the age-dependency of dose risk have been the subject of dispute; it has been suggested that the risk after exposure in middle age may be up to twice as high as currently estimated by the standard models (Dendy and Brugmans 2003; Tubiana 2005; Brenner 2009; Shuryak et al. 2010). Therefore, the authors expect that the errors in the cancer risk model are dominant over the limitations aforementioned. "
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