Analyses of cancer incidence and other morbidities in neutron irradiated B6CF1 mice

Abstract

24 The Department of Energy conduced ten large-scale neutron irradiation experiments at 25 Argonne National Laboratory between 1972 and 1989. Using a new approach to utilize 26 experimental controls to determine whether a cross comparison between experiments was 27 appropriate, we amalgamated data on neutron exposures to discover that fractionation 28 significantly improved overall survival. A more detailed investigation showed that fractionation 29 only had a significant impact on the death hazard for animals that died from solid tumors, but 30 did not significantly impact any other causes of death. Additionally, we compared the effects of 31 sex, age first irradiated, and radiation fractionation on neutron irradiated mice versus cobalt 60 32 gamma irradiated mice and found that solid tumors were the most common cause of death in 33 neutron irradiated mice, while lymphomas were the dominant cause of death in gamma 34 irradiated mice. Most animals in this study were irradiated before 150 days of age but a subset 35 of mice was first exposed to gamma or neutron irradiation over 500 days of age. Advanced age 36 played a significant role in decreasing the death hazard for neutron irradiated mice, but not for 37 gamma irradiated mice. Mice that were 500 days old before their first exposures to neutrons 38 began dying later than both sham irradiated or gamma irradiated mice. 40 INTRODUCTION 41Ionizing radiation can be classified by its linear energy transfer (LET) to better 42 understand how quickly radiation is attenuated and the concentration of energy deposited near 43 the particle track. Experiments evaluating the biological effects of low and high LET ionizing 44 radiation found that high LET radiation is more damaging to biological material in part because 3 45 sites of DNA double strand damage and other types of damage are in closer proximity to one 46 another than occurs with low LET radiation. These clusters of damage make DNA repair more 47 difficult and lead to increased cell death (1). Neutrons are the smallest and the most 48 penetrating of all particles included in the category of high LET ionizing radiation. Neutrons are 49 further classified by the amount of kinetic energy in a free neutron and this energy ranges from 50 less than 0.02eV for cold neutrons to over 20MeV for ultrafast neutrons. While numerous 51 animal studies were conducted in the USA, Europe and Asia using low LET radiation such as x-52 rays and gamma rays (2-5), extensive neutron irradiation experiments were less common. 53Between 1972 and 1989, Argonne National Laboratory (ANL) housed one of the few 54 neutron irradiators called the JANUS reactor suitable for large-scale whole-body animal 55 irradiations with fission spectrum neutrons with an energy range peak at 1 MeV (6-10). During 56 this time, ANL performed ten independent experiments investigating the effects of gamma and 57 neutron irradiations on mice. (11). These animals were irradiated under different conditions 58 and allowed to live out their entire lifespan. Ionizing radi...

Gene expression for biodosimetry and effect prediction purposes: promises, pitfalls and future directions – key session ConRad 2021

“…As described in 1.3, a study was conducted using a repository of samples and data collected in the course of large-scale animal studies between the 1950's and 1990's in the USA. Hereby it was hard to do an analysis for the animals with very low dose rates, because control animals developed cancer almost as often as LLR animals, which might be caused by the experimental stress conditions (Zander et al 2021).…”