The Linear No-Threshold Relationship Is Inconsistent with Radiation Biologic and Experimental Data

Abstract

The carcinogenic risk induced by low doses of ionizing radiation is controversial. It cannot be assessed with epidemiologic methods alone because at low doses the data are imprecise and often conflicting. Since the 1970s, the radiation protection community has estimated the risk of low doses by means of extrapolation from the risk assessed at high doses, generally by using the linear no-threshold (LNT) model. The LNT relationship implies proportionality between dose and cancer risk. This approach is based on one set of data and two hypotheses: (a) The relationship between dose and DNA damage in vivo seems linear from 1 mGy to 100 Gy with use of H2AX foci as a marker for DNA double-strand breaks (DSBs)—however, this marker is not specific (1); (b) each DSB is hypothesized to have the same probability of inducing cell transformation, irrespective of the quantity of DSBs present simultaneously in the cell; and (c) each transformed cell is hypothesized to have the same probability of developing into an invasive cancer, irrespective of the dose delivered to the tissue. The advances during the past 2 decades in radiation biology, the understanding of carcinogenesis, and the discovery of defenses against carcinogenesis challenge the LNT model, which appears obsolete (2–6). Life developed in a bath of ionizing radiation and solar ultraviolet radiation and created aerobic organisms requiring (a) defenses against the metabolically induced reactive oxygen species, (b) DNA repair, and (c) elimination of damaged cells. Several sets of data show the efficacy of these defenses to be much higher at low than at high doses and for fractionated or protracted irradiation than for acute irradiation. The LNT model was introduced as a concept to facilitate radiation protection (7). But the use of this model led to the claim that even the smallest dose (one electron traversing a cell) may initiate carcinogenesis—for instance, from diagnostic x-ray sources (8,9). This claim is highly hypothetical and has resulted in medical, economic, and other societal harm. The French Academies report (10) concluded that the LNT model and its use for assessing the risks associated with low doses are not based on scientific evidence. In contrast, the Biological Effects of Ionizing Radiation (BEIR) VII report (11) and that of the International Commission on Radiological Protection (ICRP) (12) recommended the use of the LNT model. We wish to update this debate by using recent radiation biologic and epidemiologic data.