The Increase in Animal Mortality Risk following Exposure to Sparsely Ionizing Radiation Is Not Linear Quadratic with Dose.

INTRODUCTION: The US government regulates allowable radiation exposures relying, in large part, on the seventh report from the committee to estimate the Biological Effect of Ionizing Radiation (BEIR VII), which estimated that most contemporary exposures- protracted or low-dose, carry 1.5 fold less risk of carcinogenesis and mortality per Gy than acute exposures of atomic bomb survivors. This correction is known as the dose and dose rate effectiveness factor for the life span study of atomic bomb survivors (DDREFLSS). It was calculated by applying a linear-quadratic dose response model to data from Japanese atomic bomb survivors and a limited number of animal studies. METHODS AND RESULTS: We argue that the linear-quadratic model does not provide appropriate support to estimate the risk of contemporary exposures. In this work, we re-estimated DDREFLSS using 15 animal studies that were not included in BEIR VII's original analysis. Acute exposure data led to a DDREFLSS estimate from 0.9 to 3.0. By contrast, data that included both acute and protracted exposures led to a DDREFLSS estimate from 4.8 to infinity. These two estimates are significantly different, violating the assumptions of the linear-quadratic model, which predicts that DDREFLSS values calculated in either way should be the same. CONCLUSIONS: Therefore, we propose that future estimates of the risk of protracted exposures should be based on direct comparisons of data from acute and protracted exposures, rather than from extrapolations from a linear-quadratic model. The risk of low dose exposures may be extrapolated from these protracted estimates, though we encourage ongoing debate as to whether this is the most valid approach. We also encourage efforts to enlarge the datasets used to estimate the risk of protracted exposures by including both human and animal data, carcinogenesis outcomes, a wider range of exposures, and by making more radiobiology data publicly accessible. We believe that these steps will contribute to better estimates of the risks of contemporary radiation exposures.

The effects of radiation and dose-fractionation on cancer and non-tumor disease development.

The Janus series of radiation experiments, conducted from 1970 to 1992, explored the effects of gamma and neutron radiation on animal lifespan and disease development. Data from these experiments presents an opportunity to conduct a large scale analysis of both tumor and non-tumor disease development. This work was focused on a subset of animals from the Janus series of experiments, comparing acute or fractionated exposures of gamma or neutron radiation on the hazards associated with the development of tumor and non-tumor diseases of the liver, lung, kidney or vascular system. This study also examines how the co-occurrence of non-tumor diseases may affect tumor-associated hazards. While exposure to radiation increases the hazard of dying with tumor and non-tumor diseases, dose fractionation modulates these hazards, which varies across different organ systems. Finally, the effect that concurrent non-cancer diseases have on the hazard of dying with a tumor also differs by organ system. These results highlight the complexity in the effects of radiation on the liver, lung, kidney and vascular system.