Does Scientific Evidence Support a Change From the LNT Model for Low-Dose Radiation Risk Extrapolation?

Abstract

The linear no-threshold (LNT) model has been widely used to establish international rules and standards in radiation protection. It is based on the notion that the physical energy deposition of ionizing radiation (IR) increases carcinogenic risk linearly with increasing dose (i.e., the carcinogenic effectiveness remains constant irrespective of dose) and, within a factor of two, also with dose-rate. However, recent findings have strongly put into question the LNT concept and its scientific validity, especially for very low doses and dose-rates. Low-dose effects are more difficult to ascertain than high-dose effects. Epidemiological studies usually lack sufficient statistical power to determine health risks from very low-dose exposures. In this situation, studies of the fundamental mechanisms involved help to understand and assess short- and long-term effects of low-dose IR and to evaluate low-dose radiation risks. Several lines of evidence demonstrate that low-dose and low dose-rate effects are generally lower than expected from high-dose exposures. DNA damage signaling, cell cycle checkpoint activation, DNA repair, gene and protein expression, apoptosis, and cell transformation differ qualitatively and quantitatively at high- and low-dose IR exposures, and most animal and epidemiological data support this conclusion. Thus, LNT appears to be scientifically invalid in the low-dose range.

Role of the translationally controlled tumor protein in DNA damage sensing and repair

“…Low doses of toxic agents, including chemicals and ionizing radiation, often induce protective mechanisms that enhance the ability of the organism to cope with stress from normal metabolism or exposures to exogenous agents (27). Here, we show that doses of γ rays as low as 1-10 cGy (Fig.…”

Inducible response required for repair of low-dose radiation damage in human fibroblasts

“…The validity of such a linear extrapolation from the moderate/high-dose range into the dose range of a few milligray would require that the biological processes involving the efficiency with which cells respond to the presence of DNA damage are equally efficient after low and high doses (10)(11)(12)(13). However, several radiobiological phenomena, including the bystander effect, low-dose hypersensitivity, or delayed genomic instability, challenge the assumption of a linear doseeffect relationship, although most of these studies were performed with cells in culture after moderate to high doses (14,15). Thus, their in vivo relevance in the milligray range is often unclear.…”

Limited Repair of Critical DNA Damage in Cells Exposed to Low Dose Radiation

“…To this must be added epigenetic effects, induced genome instability and the bystander effect (Mullenders et al, 2009). The factual data on these characteristics obtained for low-dose-irradiated organisms do not fit into the model of the linear dependence of biological effects on IR dose (Hayes, 2008;Averbeck, 2009;Ulsh, 2010). In this section we analyze the results of a number of independent studies on DDR development, on the signaling to activate cell cycle checkpoints and on the repair efficiency of critical DNA lesions induced by low-dose or low-intensity radiation in mammalian cells.…”