The research question provided by Feinendegen (3-7) was whether we should abandon the linear no-threshold theory for low dose radiation-induced cancer in favor of the worthwhile positive effect of radiation hormesis. To answer this question, the author reviewed the literature focusing on three main points. 1) What is the effect of low dose radiation on DNA molecules, 2) weighing the damage of DNA against the possibility of cancer and 3) the defensive protective mechanisms of the cell to radiation effect.
The author assumed that ionizing radiation as well as other non-radiation sources produce DNA damage and that reparative protective cellular mechanism overweighs the risks of exposure to low radiation doses. However, the author also assumed as DNA damage is proportional to the dose of exposure, so at higher doses the radiation effect overweighs the protective cellular mechanisms. Based on previous findings, Feinendegen (3-7) suggested the linear no-threshold theory is invalid and a hypothesis that considers linear and non-linear dose risk function should replace it. The aim of this work is to discuss, briefly, the views of radiation hormesis and the linear no-threshold hypothesis for low dose radiation-induced cancer risk. Eventually, this leads to answer the question of can accept adjusting low radiation protection policies based on lack of evidence to the linear theory and the evidence of cellular protective mechanism.
There is no controversy about health risks resulting from exposure to high doses of irradiation and authorities agree that damage induced is relevant (George 96-100). The core difference between the linear theory and radiation hormesis is twofold. First, should we look at low dose radiation as less than high doses with the same effects yet needs longer exposure or has the same effect but to a lesser degree? Alternatively, should we look at low doses with a different risk concept based on weighing the risk against cellular protective mechanism? (George 96-100).
The basis of the linear no-threshold theory is the simple hypothesis that when one particle of a radiating substance strikes a targeted DNA molecule in the nucleus of one human cell, it can initiate carcinogenicity. In other words, if we assume that cancer risk of 100 rad dose is X, then a dose of 1 rad produces cancer risk of 0.01 X risk. Therefore, zero risks can at no time exists (Cohen 1137). Brenner and Raabe (279-285), stated there exists bulky epidemiological and laboratory evidence literature as regards cell mutations and gene aberrations, on exposure to radiation dose of 100 mGy to 1 Gy and from 10 mg to 1 Gy (for epidemiological and laboratory studies respectively). However, for smaller doses (for example from below 10 mGy to 100 mGy) scientists do not know the dose-effect pattern of the risk curve. Moreover, for these smaller doses, the ultimatum of gene aberration is still obscure, that is carcinoma or sarcoma or which type of malignancy (lung, breast, bone, leukemia…etc) may be induced. Therefore, for such lower doses, the basis of all arguments depends on known biophysical information.
The basic information for the linear no-threshold theory is; high doses of radiation induce cell and DNA changes enough to start a process of carcinogenesis. Moreover, on reducing the dose (low radiation dose), only the number of cells subjected to damage is decreased but damage occurs in these fewer cells. Knowing that tumors are mainly of monoclonal origin, it is reasonable to assume that a linear relationship exists between radiation exposure and the risk of radiation-induced cancer. Brenner and Sachs (253-256), stated that there is no enough epidemiological data for the risk of low radiation exposure (equal to or less than 1 mGy). Therefore, the aim of linear hypothesis is to assess low dose radiation risk using the available epidemiological data for higher doses (yet still considered low) to establish a fixed point then infer cancer risk down from this point. This theory is opposed by the adaptive and protective responses of cells exposed to low-dose radiation. Feinendegen (3-7) summarized these responses into three categories. 1) Stimulation of detoxification of reactive oxygen species occurs few hours after exposure and lasts from few hours to few weeks, thus preventing cell damage. 2) Eliminating damaged cells by apoptosis (a type of cell death to give way to newly regenerating cells), and 3) the process of immune surveillance attacking the mutated cells considered as foreign cells. Despite these facts, absence of quantification of these biological processes keeps the linear theory argument viable.
The concept of low dose radiation hormesis is exposure to low doses of radiation produces activation in cells, tissues and organs as a result of stimulation of indigenous mechanisms whereas exposure to high radiation doses inhibits these mechanisms (Luckey 22-40). Luckey (22-40) reviewed 3000 reports on cell stimulation produced by low dose radiation doses and stated that animal experiments, as well as human experiences, show benefits from exposure to low doses of radiation, a phenomenon he called radiogenic metabolism. Yet, the author did not provide data from experiments on mammals. Luckey (22-40) assumes that exposure to low doses of radiation particularly stimulates the immune system for better performance and the reproduction process. Preston, in his lecture, stated that it is reasonable to, qualitatively, foresee tumor outcomes from the currently available data of the effects of ionizing radiation on DNA aberrations. Preston added the dose-effect curves for such aberrations are linear at low doses, and tumor risk assessment should depend on tumor frequencies and not on explaining cell behavior on mechanical considerations. Supportive evidence for the low-dose radiation hormesis concept is doses used in oncological radiotherapy. Whereas massive doses of 4000-6000 rads used in the treatment of some malignancies are debilitating, smaller doses of 150 rads on divided doses may lead to survival rates of up to 12 years (Kauffman 406).
Feinendegen (3-7) suggested that the linear no-threshold theory of low dose radiation risk is invalid and it is time to replace it with another that considers both linear and non-linear dose-risk function for radiological protection standard measures. Yet, no radiation hormesis study, including that of Feinendegen, suggested at what level the threshold should be or quantified the cell adaptive responses. The effect of low dose radiation is at least difficult to predict, therefore it is not safe to infer beneficial or harmful injurious effects, and it might be more reasonable to assume that either effect are theoretically possible. An established fact is whatever effect depends mainly on the dose and the number of cells affected and as biological processes vary; there should a difference between the human being as a unit and the behavior of individual cells. For radiation low dose effects, the consequences of the human being should predominate over the predominating events of individual cells.
In conclusion, the linear no-threshold theory should continue as the main guideline for standard radiation protection measures. Consequently, the principle of (As Low As Reasonably Achievable) ALARA currently adopted for radiation protection standards should remain essential for radiation protection measures especially that there is no conclusive data strongly suggesting other perceptions. It is likely the debate will continue, as there are other factors that need to be included in the risk assessment as the type of radiation, dose rate and fractionation, dose distribution, dietary factors, and radiation carcinogenesis modifying factors. In absence of a conclusive radiobiological data and quantification of cellular and tissue response in modifying radiation effects, one can expect that health risk might be overestimated, however, the low probability of carcinogenic transformations and the presence of cell defensive mechanism, are somewhat reassuring.
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Georges L. D. Low-dose ionizing radiation exposure: Understanding the risk for cellular transformation. Journal of Biological Regulators and Homeostatic Agents. Vol. 18. (2004). 96-100.
Cohen B.L. Cancer Risk from Low Level Radiation. American Journal of Roentgenology. Vol. 179 (5). (2002). 1137-1143.
Brenner D. J. and Raabe O. G. Is The Linear-No-Threshold Hypothesis Appropriate For Use In Radiation Protection? Radiation Protection Dosimetry. Vol. 79. (2001). 279-285.
Brenner D. J. and Sachs R. K. Estimating radiation-induced cancer risks at very low doses: rationale for using a linear no-threshold approach. Radiat Environment Biophys. Vol. 44. (2006). 253-256.
Luckey T. D. Radiation Hormesis Overview. RSO Magazine. Vol. 8 (4). (2003). p. 22-40.
Preston, R. J. Carcinogenic Effects of Low Doses of Ionizing Radiation: EIMS Metadata Report. American Association for the Advancement of Science. Environmental Information Management System. Washington, Seattle. 2004. Web.
Kauffman J M. Radiation Hormesis: Demonstrated, Deconstructed, Denied, Dismissed, and Some implications for public Policy. J. Scientific Exploration. 17 (3). (2003): 389-407.