Long-Term Followup of the Delayed Effects of Acute Radiation Exposure in Primates
Abstract
Following the end of World War II, the atomic bomb explosions generated significant interest in how radiation damages living organisms. It has become clear through studies of the survivors of Hiroshima and Nagasaki that the long-term effects of radiation exposure include not only increased cancer risk, but also increased risk of heart disease and a variety of other illnesses. A large body of research was done in the 1950s and 1960s, before the modern era of molecular biology. However, the full extent of the long-term health effects of radiation remains unknown. Following the terrorist attacks on 9/11, interest in radiation effects was renewed due to the potential for nuclear terrorism. In light of our current understanding of cellular biology, metabolism, and genetics, there is the potential to make substantial progress in preventing and treating the effects of radiation exposure. This has led to many studies being done in monkeys because they are genetically and physiologically similar to human beings. Over the past 9 years, we have been privileged to serve as the national repository of previously irradiated monkeys, which have been donated to Wake Forest University by several research groups. These animals have been given high doses of radiation in order to study ways to mitigate radiation injury. After "adopting" them into our long-term Radiation Survivor Cohort, we have begun to study them for delayed effects of radiation, with a degree of scientific intensity that has not been undertaken before in humans or animals. This work is supported by the National Institutes of Health. These animals are a unique and priceless resource for studies of short-term and long-term effects of radiation exposure. We have noted three surprising problems in these animals: (1) an increased risk of diabetes; (2) scarring of the heart muscle leading to heart failure; and (3) "blind spots" in their immune systems such that they are unable to build a protective response to infection after vaccination. All three of these problems relate to common medical problems that have high relevance to active military personnel, Veterans, and their dependents. In order to address these highly relevant health risks in the most productive way possible, we propose four projects. Project 1: Mechanisms of Diabetes Development in Irradiated Nonhuman Primates. The goal of this study is to understand the molecular mechanisms by which radiation causes diabetes and whether they are similar to or different from diabetes occurring spontaneously without radiation; this will help us to determine how to treat this disease. Project 2: Radiation-Induced Heart Disease. This project seeks to determine the cause and mechanism for radiation-induced scarring of the heart and whether this is related to inflammation, cell death, or some other process and to determine whether there is any evidence the long-term cohort or other ongoing studies for potentially effective treatment or prevention of this disease. Project 3: Immunological Injury and Recovery. This project will further explore the immune "blind spots" and whether the body can recover from the immune injury with or without treatment and will examine specific drugs (growth factors) that may assist recovery. Project 4: Genetic and Genomic Signatures of Long-Term Radiation Exposure in Non-Human Primates. This project provides a genetic "underpinning" for the other three projects, by examining the same animals used in projects 1-3 for radiation-induced DNA mutations and other genetic injuries that may affect diabetes, heart disease, or immunity. In the short term, these projects will provide knowledge regarding how and why these diseases occur after radiation exposure. In the long term, they will lead to the development of therapies to prevent or treat these serious conditions in human patients exposed to radiation.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Apr 04, 2016
- Source ID
- W81XWH1510574
Entities
People
- J. Cline
Organizations
- United States Army
- Wake Forest University