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that early life systemic radiation injury affects the lung’s response differentially as compared to the
mature lung. Furthermore, that early life systemic radiation induces unique responses as compared to
early life external irradiation injury. Funded By: R01 AI101732-01, U19AI091036, P30 ES-01247 and ES
T32 07026.
(PS2-49) Effects of pulmonary clearance associated with radiation injury to the lung. Carl J. Johnston,
Ph.D; Jacqueline P. Williams, Ph.D; Robert Gelein, MS; Jacob N. Finkelstein, PhD, University of Rochester
Medical Center, Rochester, NY
The most likely source of radioactive contamination results for the detonation of an explosive
device that is packed with a radioactive isotope. This so-called “dirty bomb” results in the generation of a
radioactive aerosol that leads to both surface and systemic exposure. The internal exposure results from
the inhalation of particles generated by such an explosive device. Methods: 8 week old female C57Bl/6
mice were irradiated with either 0 Gy or 12.5 Gy whole lung. Mice immediately placed in individual wire
mesh cages and exposed to TiO2 (Fisher) aerosol for 4 hours. The MMAD of the TiO2 was 1.21 uM. Mice
were then examined immediately after exposure as well as 4 and 8 weeks post exposure. Results: The
TiO2 lung burden in the 0 Gy + TiO2 mice and the 12.5 Gy + TiO2 mice was 18 ug / lung immediately after
exposure. 4 weeks post irradiation 0 Gy + TiO2 mice was 5.25 ug/lung whereas the 12.5 Gy + TiO2 mice
was 7.23 ug/lung. Examination of messages encoding MCP-1, IL-1b and KC demonstrated a 3-4 fold
increase in the 4 week mice exposed to 12.5 Gy + Tio2 as compared to the 0 Gy + TiO2 4 weeks post
irradiation. Conclusion: Mice that were irradiated retained a higher concentration of particles suggesting
that these lungs would receive a higher dose of irradiation for a prolonged period of time. Supported by
R01 AI101732-01, U19AI091036, P30 ES-01247 and ES T32 07026.
(PS2-50) Ionizing Radiation Elicits a Significant Loss of Lean Body Mass and Activation of the Catabolic
Program in Skeletal Muscle via an Indirect Mechanism Involving Systemic Inflammation. Theodore P.
Braun, PhD; Marek Szumowski; Steve Rhodes; James Tanyi; Anupriya Agarwal; Charles R. Thomas, MD;
and Daniel L. Marks, MD, PhD, Oregon Health & Science University, Portland, OR
Purpose: During the course of cancer treatment, patients frequently experience a decline in performance
status. The accompanying weakness and lethargy are manifestation wasting syndrome known as cancer
cachexia, which is defined by a loss of skeletal muscle mass. The development of cachexia seriously limits
the ability to administer full-dose and potentially curative therapy regardless of modality. This occurs as
a result of both tumor growth and cancer treatment. The mechanism linking radiation treatment to
cachexia has not been well described, limiting the development of therapeutic approaches. Methods: We
developed a model of murine radiation therapy, allowing for the delivery of radiation to the thorax while
shielding the head and hind limbs. This allows for the investigation of the indirect effects of ionizing
radiation on behavior and muscle metabolism. We treated C57BL/6J mice with a single dose of 20 Gy
delivered to the thorax, and assessed them after 18 hours. Food intake, body weight and body
composition were assessed. Serum cytokine levels were measured by multiplex bead based assay. Real-
Time PCR was utilized to assess the activation of the ubiquitin proteasome system in skeletal muscle.
Results: We found that localized irradiation produced systemic inflammation marked by an increase in the
circulating level of the cytokine CXCL10. Animals receiving radiation consumed less food and lost a
162 | P a g e
mature lung. Furthermore, that early life systemic radiation induces unique responses as compared to
early life external irradiation injury. Funded By: R01 AI101732-01, U19AI091036, P30 ES-01247 and ES
T32 07026.
(PS2-49) Effects of pulmonary clearance associated with radiation injury to the lung. Carl J. Johnston,
Ph.D; Jacqueline P. Williams, Ph.D; Robert Gelein, MS; Jacob N. Finkelstein, PhD, University of Rochester
Medical Center, Rochester, NY
The most likely source of radioactive contamination results for the detonation of an explosive
device that is packed with a radioactive isotope. This so-called “dirty bomb” results in the generation of a
radioactive aerosol that leads to both surface and systemic exposure. The internal exposure results from
the inhalation of particles generated by such an explosive device. Methods: 8 week old female C57Bl/6
mice were irradiated with either 0 Gy or 12.5 Gy whole lung. Mice immediately placed in individual wire
mesh cages and exposed to TiO2 (Fisher) aerosol for 4 hours. The MMAD of the TiO2 was 1.21 uM. Mice
were then examined immediately after exposure as well as 4 and 8 weeks post exposure. Results: The
TiO2 lung burden in the 0 Gy + TiO2 mice and the 12.5 Gy + TiO2 mice was 18 ug / lung immediately after
exposure. 4 weeks post irradiation 0 Gy + TiO2 mice was 5.25 ug/lung whereas the 12.5 Gy + TiO2 mice
was 7.23 ug/lung. Examination of messages encoding MCP-1, IL-1b and KC demonstrated a 3-4 fold
increase in the 4 week mice exposed to 12.5 Gy + Tio2 as compared to the 0 Gy + TiO2 4 weeks post
irradiation. Conclusion: Mice that were irradiated retained a higher concentration of particles suggesting
that these lungs would receive a higher dose of irradiation for a prolonged period of time. Supported by
R01 AI101732-01, U19AI091036, P30 ES-01247 and ES T32 07026.
(PS2-50) Ionizing Radiation Elicits a Significant Loss of Lean Body Mass and Activation of the Catabolic
Program in Skeletal Muscle via an Indirect Mechanism Involving Systemic Inflammation. Theodore P.
Braun, PhD; Marek Szumowski; Steve Rhodes; James Tanyi; Anupriya Agarwal; Charles R. Thomas, MD;
and Daniel L. Marks, MD, PhD, Oregon Health & Science University, Portland, OR
Purpose: During the course of cancer treatment, patients frequently experience a decline in performance
status. The accompanying weakness and lethargy are manifestation wasting syndrome known as cancer
cachexia, which is defined by a loss of skeletal muscle mass. The development of cachexia seriously limits
the ability to administer full-dose and potentially curative therapy regardless of modality. This occurs as
a result of both tumor growth and cancer treatment. The mechanism linking radiation treatment to
cachexia has not been well described, limiting the development of therapeutic approaches. Methods: We
developed a model of murine radiation therapy, allowing for the delivery of radiation to the thorax while
shielding the head and hind limbs. This allows for the investigation of the indirect effects of ionizing
radiation on behavior and muscle metabolism. We treated C57BL/6J mice with a single dose of 20 Gy
delivered to the thorax, and assessed them after 18 hours. Food intake, body weight and body
composition were assessed. Serum cytokine levels were measured by multiplex bead based assay. Real-
Time PCR was utilized to assess the activation of the ubiquitin proteasome system in skeletal muscle.
Results: We found that localized irradiation produced systemic inflammation marked by an increase in the
circulating level of the cytokine CXCL10. Animals receiving radiation consumed less food and lost a
162 | P a g e
