Low-dose radiation risk extrapolation fallacy associated with the linear-no-threshold model

Abstract

Managing radiation risks typically involves establishing regulations that limit radiation exposure. The linear-no-threshold (LNT) dose—response model has been the traditional regulatory default assumption. According to the LNT model, for low a linear-energy-transfer (LET) radiation-induced stochastic effects (e.g., neoplastic transformation and cancer), the risk increases linearly without a threshold. Any radiation exposure is predicted to increase the number of cancer cases among a large population of people. Cancer risk extrapolation from high to low doses based on this model is widespread. Here, indirect evidence is provided that the excess cancer risk calculated at very low doses of low-LET radiation (e.g., around 1 mGy), based on extrapolating from high dose data for an irradiated human population using the LNT model, is likely a phantom excess risk. Indirect evidence is provided, suggesting that for brief exposures to low-LET radiation doses on the order of 1 mGy, that a decrease below the spontaneous level is many orders of magnitude more probable than for any increase in risk as would be predicted by extrapolating from high to low doses using the LNT model. Such a decrease is, however, not expected after exposure to high-LET alpha radiation. The risk reduction has been largely attributed to the induction of a protective apoptosis-mediated (PAM) process that selectively eliminates cells that contain genomic instability (e.g., mutant and neoplastically transformed cells). The PAM process appears to require a dose-rate-dependent stochastic threshold for activation whose minimum is estimated to possibly be as low as 0.01 mGy for X-rays and gamma rays. However, if the dose is too high (e.g., above 250mGy for brief exposure at a high rate to X-rays or gamma rays), the PAM process is not expected to be activated. For protracted exposure to X-rays or gamma rays, doses as high as 400 mGy (and possibly higher) may activate the PAM process.

Keywords

radiation risk assessment LNT hormesis

References

Higson DJ The bell tolls for LNT. Oper. Radiat Safety 2004; 87(5): S47-S50.

Calabrese EJ , Baldwin LA The hormetic dose- response model is more common than the threshold model in toxicology. Toxicol Sci 2003; 71: 246-50.

Feinendegen LE Low doses of ionizing radiation: relationship between biological benefit and damage induction. World J Nucl Med 2005; 4: 21-34.

Azzam EI , de Toledo SM , Little JB Stress signaling from irradiated to non-irradiated cells. Curr Cancer Drug Target 2004; 4: 53-64.

Scott BR A biological-based model that links genomic instability, bystander effects, and adaptive response. Fundamental and Molecular Mechanisms of Mutagenesis , Mut Res 2004; 568: 129-43.

Scott BR NEOTRANS3 Model for low-dose-induced stochastic radiobiological effects . Poster presentation given at the Department of Energy, Low Dose Radiation Research Program Workshop V, Hyatt Regency, Bethesda, MD, April 25-27, 2005. Retrieved from http://www.radiation-scott.org/Scott_4C_for_web.pdf

Scott BR Low-dose radiation-induced protective process and implications for risk assessment, cancer prevention, and cancer therapy. Dose-Response 2007; 5(2): 131-141.

Hooker AM , Bhat M. , Day TK , Lane JM , Swinburne SJ , Morley AA , Sykes PJ The linear no-threshold model does 1not hold for low-dose ionizing radiation . Radiat Res 2004; 162: 447-52.

Redpath JL , Liang D. , Taylor TH , James C. , Christie E. , Elmore E. The shape of the dose-response curve for radiation-induced neoplastic transformation in vitro: evidence for an adaptive response against neoplastic transformation at low doses of low-LET radiation. Radiat Res 2001; 156: 700-7.

10.

Azzam EI , de Toledo SM , Raaphorst GP , Mitchel RE Low-dose ionizing radiation deceases the frequency of neoplastic transformation to a level below the spontaneous rate in C3H 10T1/2 cells. Radiat Res 1996; 146: 369-73.

11.

Ko SJ , Liao X. -Y, Molloi S. , Elmore E. , Redpath JL Neoplastic transformation in vitro after exposure to low doses of mammographic-energy x rays: quantitative and mechanistic aspects. Radiat Res 2004; 162: 646-54.

12.

Redpath JL , Lu Q. , Lao X. , Molloi S. , Elmore E. Low doses of diagnostic energy x-rays protect against neoplastic transformation in vitro. Int J Radiat Biol 2003; 79(4): 235-40.

13.

Chen WL , Luan YC , Shieh MC , Chen ST , Kung HT , Soong KL , Yeh YC , Chou TS , Mong SH , Wu JT , Sun CP , Deng WP , Wu MF , Shen ML Is chronic radiation an effective prophylaxis against cancer? J Am Phys Surg 2004; 9(1): 6-10.