Accession Number:

ADA533715

Title:

Radiation Combined Injury: DNA Damage, Apoptosis, and Autophagy

Descriptive Note:

Journal article

Corporate Author:

ARMED FORCES RADIOBIOLOGY RESEARCH INST BETHESDA MD

Report Date:

2010-01-01

Pagination or Media Count:

11.0

Abstract:

Radiation combined injury is defined as an ionizing radiation exposure received in combination with other trauma or physiological insults. The range of radiation threats we face today includes everything from individual radiation exposures to mass casualties resulting from a terrorist nuclear incident, and many of these exposure scenarios include the likelihood of additional traumatic injury. Radiation combined injury sensitizes target organs and cells and exacerbates acute radiation syndrome. Organs and cells with high sensitivity to combined injury are the skin, the hematopoietic system, the gastrointestinal tract, spermatogenic cells, and the vascular system. Among its many effects, radiation combined injury results in decreases in lymphocytes, macrophages, neutrophils, platelets, stem cells, and tissue integrity activation of the iNOSNF-BNF-IL6 and p53Bax pathways and increases in DNA single and double strand breaks, TLR signaling, cytokine concentrations, bacterial infection, and cytochrome c release from mitochondria to cytoplasm. These alterations lead to apoptosis and autophagy and, as a result, increased mortality. There is a pressing need to understand more about the bodys response to combined injury in order to be able to develop effective countermeasures, since few currently exist. In this review, we summarize what is known about how combined injury modifies the radiation response, with a special emphasis on DNA damagerepair, signal transduction pathways, apoptosis, and autophagy. We also describe current and prospective countermeasures relevant to the treatment and prevention of combined injury.

Subject Categories:

  • Radiobiology

Distribution Statement:

APPROVED FOR PUBLIC RELEASE