Radiation-induced death : characterization of a novel mechanism / Gabriel Stuart Krigsfeld.

Format:

Book

Manuscript

Thesis/Dissertation

Author/Creator:

Krigsfeld, Gabriel Stuart.

Contributor:

Kennedy, Ann R., advisor.

Arruda, Valder R., committee member.

Camire, Rodney M., committee member.

Cengel, Keith A., committee member.

Ischiropoulos, Harry, committee member.

University of Pennsylvania. Pharmacology.

Language:

English

Subjects (All):

Penn dissertations--Pharmacology.

Pharmacology--Penn dissertations.

Local Subjects:

Penn dissertations--Pharmacology.

Pharmacology--Penn dissertations.

Physical Description:

xiii, 183 pages : color illustrations ; 29 cm

Production:

2013.

Summary:

Astronauts traveling to Mars will be exposed to Solar Particle Events (SPEs) during their missions. Modeling these large SPEs has led to the knowledge that such SPEs can result in significant doses of radiation that could be deleterious to astronaut health and mission success. Since the bombings of Hiroshima and Nagasaki in 1945, an emphasis has been placed on understanding the consequences of ionizing radiation. At the lowest doses of radiation known to be capable of killing mammals, radiation-induced death is hypothesized to occur due to the hematopoietic syndrome through a severe loss of cells in the hematopoietic system that potentially results in infection (from the loss of white blood cells) and bleeding (from the loss of platelets). The lethal dose of radiation to 50% of the population, referred to as the LD50, for the Hiroshima and Nagasaki casualties is calculated to be ∼2.5 Gy. Certain animals have LD50 values as low as 1.4 Gy (cattle) and as high as 13.4 Gy (mice). The differences in the LD 50 between species have yet to be explained. In these studies, animals were exposed to doses of radiation near the LD50 and monitored for parameters as part of hemostasis and the hematopoietic system. This work will focus on the mechanism of radiation-induced death by evaluating both the hematopoietic system and hemostasis (primary and secondary). Radiation exposure resulted in activation of blood clotting parameters within hours of exposure; this activation persisted, and became more abnormal over time. The results presented here suggest that the cell killing effects of radiation in white blood cells or platelets may not be responsible for death in mammals at the LD50, but, in fact, are due to disseminated intravascular coagulation (DIC). We hypothesize that the mechanism by which mammals die from low doses of radiation is determined by their propensity to develop DIC, which determines their LD50. These results suggest a novel mechanism to describe the mechanism by which humans die at the LD50 and provide insight into the variable LD50 values observed among mammals. These studies will provide new direction for our understanding and treatment of radiation exposure.

Notes:

Adviser: Ann R. Kennedy.

Thesis (Ph.D. in Pharmacology) -- University of Pennsylvania, 2013.

Includes bibliographical references.

OCLC:

862507782