The Effects of Radiation and Dose-Fractionation on Cancer and Non-Tumor Disease Development

William Liu,Jian-Jian Li,Gayle Woloschak,Tatjana Paunesku,David Grdina,Benjamin Haley,Mary Kwasny

doi:10.3390/ijerph9124688

Abstract

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.

Highlights

Epidemiologic studies of radiation exposure on human populations have been limited to non-experimental ecological, cohort, and case-control studies
“non-lethal” variants of a particular pathology were combined, to form an overall pathology outcome for each animal. We favored this approach primarily because of the inherent subjectivity in assigning a probable cause of death, and that the proctors were under the requirement to assign a single most probable cause of death to each animal, precluding the possibility of assigning multiple organ dysfunction (MODS) as a cause of mortality [19]
* indicates that the particular model did not satisfy the proportional hazards assumption. With such a large and comprehensively documented database of controlled radiobiology experiments, the Janus series of experiments presents a rare opportunity to evaluate the pathological effects of radiation on animals

Summary

Introduction

Epidemiologic studies of radiation exposure on human populations have been limited to non-experimental ecological, cohort, and case-control studies. These studies have largely focused on radiation workers [1,2], individuals accidentally exposed to radiation through nuclear accidents (Chernobyl [3]), or atomic bomb survivors [4]. There have been studies suggesting that there exists a link between cardiovascular based mortality and morbidity after radiation exposure in patients with breast cancer [2]. This is due, presumably, to the proximity of the radiation treatment field to the heart and critical veins/arteries. Other non-tumor diseases, including liver disease [8]

Methods

Results

Conclusion