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prior to irradiation; however use as a radioprotectant in the human population would require the
supplement to mitigate radiation-induced damage when taken following irradiation. We will present data
comparing the protective effects of our standard supplement regime (given 30d prior to, and for the
duration of post-irradiation study) to mice supplemented only in the post-irradiation period. Tissue and
blood samples were collected 2, 30 and 120 days post-irradiation and analyzed for markers of oxidative
damage, antioxidant status and a panel of pro- and anti-inflammatory cytokines. At all timepoints tested,
mice fed the supplement prior to irradiation had significant reductions in oxidative DNA damage and
serum inflammatory markers, while showing increases in cellular antioxidant capacity. The supplement
still provided significant protection when given post-irradiation; however the magnitude of protection
was more variable. The effects of our complex dietary supplement as an effective radioprotectant
following irradiation will be discussed.
(PS6-44) A model of radiation-induced cachexia in the nonhuman primate. Wanchang Cui; Alexander
Bennett; Pei Zhang; Kory Barrow; Sean Kearney; Kim Hankey; Cheryl Taylor-Howell; Thomas J. MacVittie
University of Maryland Baltimore, Baltimore, MD
Background and Aims: Radiation therapy has been associated with anorexia and weight loss, thus
severely affecting the patients’ quality of life and may even lead to death. Animal models of radiation-
induced cachexia that enable testing of therapeutic drugs are urgently needed. We are assessing a
nonhuman primate (NHP) radiation-induced cachexia model that may allow insights into the molecular
changes contributing to the disease. Methods: NHP were exposed to 10 or 11Gy partial-body irradiation
to assess the efficacy of radiation medical countermeasures. All animals received supportive care. Clinical
parameters including complete blood counts, body weights and core body temperatures. CT imaging (3rd
lumbar vertebrae) was acquired at different time points to quantify skeletal muscle volume change.
Skeletal muscle tissues were collected at the time of euthanasia for molecular and histological studies.
Results: We observed severe cases of cachexia, 25% loss of body weight after radiation exposure. CT
imaging indicated that these animals may lose as much as 50% skeletal muscle volume at time of
maximum body weight loss. Histological staining showed abnormalities such as inflammation, adipocyte
replacement, deranged muscle fibers, etc in irradiated muscle tissues. Additionally, multiple components
of the protein catabolism pathway such as ubiquitin, Atrogin-1 and MuRF1 were significantly increased in
cachectic animals. These results are in agreement with the ubiquitin-proteasome system’s role in the
breakdown of the bulk of muscle proteins and the accelerated muscle proteolysis. To investigate whether
the ActRIIB pathway was elevated in our NHP model, we measured the mRNA levels of ActRIIB and
myostatin. ActRIIB levels were significantly increased while myostatin levels were decreased in the
cachectic animals. Conclusion: In summary, these data herein suggested protein catabolism and ActRIIB
pathways may play important roles in severe radiation-induced cachexia. This work was supported by
NIAID contract HHSN272202000046C.
348 | P a g e
supplement to mitigate radiation-induced damage when taken following irradiation. We will present data
comparing the protective effects of our standard supplement regime (given 30d prior to, and for the
duration of post-irradiation study) to mice supplemented only in the post-irradiation period. Tissue and
blood samples were collected 2, 30 and 120 days post-irradiation and analyzed for markers of oxidative
damage, antioxidant status and a panel of pro- and anti-inflammatory cytokines. At all timepoints tested,
mice fed the supplement prior to irradiation had significant reductions in oxidative DNA damage and
serum inflammatory markers, while showing increases in cellular antioxidant capacity. The supplement
still provided significant protection when given post-irradiation; however the magnitude of protection
was more variable. The effects of our complex dietary supplement as an effective radioprotectant
following irradiation will be discussed.
(PS6-44) A model of radiation-induced cachexia in the nonhuman primate. Wanchang Cui; Alexander
Bennett; Pei Zhang; Kory Barrow; Sean Kearney; Kim Hankey; Cheryl Taylor-Howell; Thomas J. MacVittie
University of Maryland Baltimore, Baltimore, MD
Background and Aims: Radiation therapy has been associated with anorexia and weight loss, thus
severely affecting the patients’ quality of life and may even lead to death. Animal models of radiation-
induced cachexia that enable testing of therapeutic drugs are urgently needed. We are assessing a
nonhuman primate (NHP) radiation-induced cachexia model that may allow insights into the molecular
changes contributing to the disease. Methods: NHP were exposed to 10 or 11Gy partial-body irradiation
to assess the efficacy of radiation medical countermeasures. All animals received supportive care. Clinical
parameters including complete blood counts, body weights and core body temperatures. CT imaging (3rd
lumbar vertebrae) was acquired at different time points to quantify skeletal muscle volume change.
Skeletal muscle tissues were collected at the time of euthanasia for molecular and histological studies.
Results: We observed severe cases of cachexia, 25% loss of body weight after radiation exposure. CT
imaging indicated that these animals may lose as much as 50% skeletal muscle volume at time of
maximum body weight loss. Histological staining showed abnormalities such as inflammation, adipocyte
replacement, deranged muscle fibers, etc in irradiated muscle tissues. Additionally, multiple components
of the protein catabolism pathway such as ubiquitin, Atrogin-1 and MuRF1 were significantly increased in
cachectic animals. These results are in agreement with the ubiquitin-proteasome system’s role in the
breakdown of the bulk of muscle proteins and the accelerated muscle proteolysis. To investigate whether
the ActRIIB pathway was elevated in our NHP model, we measured the mRNA levels of ActRIIB and
myostatin. ActRIIB levels were significantly increased while myostatin levels were decreased in the
cachectic animals. Conclusion: In summary, these data herein suggested protein catabolism and ActRIIB
pathways may play important roles in severe radiation-induced cachexia. This work was supported by
NIAID contract HHSN272202000046C.
348 | P a g e
