Molecular and Cellular Biology of Moderate-Dose (1–10 Gy) Radiation and Potential Mechanisms of Radiation Protection: Report of a Workshop at Bethesda, Maryland, December 17–18, 2001¹

Abstract

Exposures to doses of radiation of 1-10 Gy, defined in this workshop as moderate-dose radiation, may occur during the course of radiation therapy or as the result of radiation accidents or nuclear/radiological terrorism alone or in conjunction with bioterrorism. The resulting radiation injuries would be due to a series of molecular, cellular, tissue and whole-animal processes. To address the status of research on these issues, a broad-based workshop was convened. The specific recommendations were: (1) RESEARCH: Identify the key molecular, cellular and tissue pathways that lead from the initial molecular lesions to immediate and delayed injury. The latter is a chronic progressive process for which postexposure treatment may be possible. (2) Technology: Develop high-throughput technology for studying gene, protein and other biochemical expression after radiation exposure, and cytogenetic markers of radiation exposure employing rapid and accurate techniques for analyzing multiple samples. (3) Treatment strategies: Identify additional biological targets and develop effective treatments for radiation injury. (4) Ensuring sufficient expertise: Recruit and train investigators from such fields as radiation biology, cancer biology, molecular biology, cellular biology and wound healing, and encourage collaboration on interdisciplinary research on the mechanisms and treatment of radiation injury. Communicate knowledge of the effects of radiation exposure to the general public and to investigators, policy makers and agencies involved in response to nuclear accidents/events and protection/treatment of the general public.

Radiation as a Risk Factor for Cardiovascular Disease

“…The extent to which exposure to 10 Gy TBI, a potentially survivable dose in a radiation accident or radiological terrorism event (22), could result in injury to the cardiovascular system is unknown. In this situation, the entire body rather than a single organ such as the heart would be exposed to a single, possibly heterogeneous dose of radiation.…”

“…There is an immediate need for a practical therapy to prevent, mitigate, and/or treat radiation-induced injury to the heart after irradiation (22). The U.S. National Institutes of …”

Effect of Gamma Ray on Reactive Oxygen Species at Experimental Animals

“…The deleterious effects of ionizing radiation in biological systems are mainly mediated through the generation of reactive oxygen species (ROS) in cells as a result of water radiolysis [6]. ROS and oxidative stress may contribute to radiation-induced cytotoxicity and to metabolic and morphologic changes in animals and humans during radiotherapy, experimentation, or even space flight [7].…”

Protection against Radiation-Induced Bone Marrow and Intestinal Injuries by Cordyceps sinensis, a Chinese Herbal Medicine

“…In principle, endogenous hematopoietic recovery could occur in humans after exposures to up to 9 or 10 Gy (single fraction); however, an extended period of pancytopenia begins as early as 4 to 7 days after significantly lower doses (13) and, to survive, a prolonged regimen of intensive supportive care, including broad-spectrum antibiotics and frequent transfusion of blood components, must be administered. Despite improvements in supportive care together with treatment using cytokines such as granulocyte colony-stimulating factor (G-CSF) ANIMAL MODELS FOR MEDICAL COUNTERMEASURES 561 and stem cell factor (SCF), mortality from accidental radiation exposures of .5 Gy remains high (39,48). One explanation is the increased risk of overwhelming opportunistic infections, primarily bacterial pathogens translocated from the gastrointestinal tract.…”