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

Abstract

26With increasing medical radiation exposures, it is important to understand how 27 different modes of delivery of ionizing radiation as well as total doses of exposure impact 28 health outcomes. Our lab studied the risks associated with ionizing radiation by analyzing the 29 Northwestern University Radiation Archive for animals (NURA). NURA contains detailed data 30 from a series of 10 individual neutron and gamma irradiation experiments conducted on over 31 50,000 mice. Rigorous statistical testing on control mice from all Janus experiments enabled us 32 to select studies that could be compared to one another and uncover unexpected differences 33 among the controls as well as experimental animals. For controls, mice sham irradiated with 34 300 fractions died significantly earlier than those with fewer sham fractions. Using the 35 integrated dataset of gamma irradiated and control mice, we found that fractionation 36 significantly decreased the death hazard for animals dying of lymphomas, tumors, non-tumors, 37 and unknown causes. Gender differences in frequencies of causes of death were identified 38 irrespective of irradiation and dose fractionation, with female mice being at a greater risk for all 39 causes of death, except for lung tumors. Irradiated and control male mice were at a significantly 40 greater risk for lung tumors, the opposite from observations noted in humans. Additionally, we 41 discovered that lymphoma deaths can occur quickly after exposures to high doses of gamma 42 rays. This study systematically cross-compared outcomes of different modes of fractionation 43 across a wide span of total doses to demonstrate that protraction modulated survival and 44 disease status differently based on the total dose, cause of death, and sex of an animal. This 45 novel method for analyzing the Janus datasets will lead to insightful new mechanistic 46 hypotheses and research in the fields of radiation biology and protection.49 impacts is important for setting radiation protection standards. Approximately half of 50 humankind's cumulative annual radiation exposure comes from natural sources, such as cosmic 51 radiation and soil; the other half is derived from human-made sources including medical 52 procedures and nuclear medicine (1). Most of the general population receives low dose chronic 53 ionizing radiation exposures, accumulating to a few hundred mSv over a lifetime (2). 54Calculating the risks associated with these chronic exposures is challenging because of 55 the high background levels for the same diseases ionizing radiation can induce and the low 56 overall effect of these lower dose/dose-rate exposures. There are several helpful data sources 57 that researchers have utilized to help quantify these risks including radiation therapy studies, 58 atomic bomb survivor data, and other epidemiological studies from workers in the field and 59 nuclear disasters. The radiation doses given to patients for radiation therapy are much larger 60 than standard exposure and are only used on a small segmen...