Page 374 - 2014 Printable Abstract Book
P. 374
(PS7-37) Epigenetic memories of DNA repair induced by low or high let-radiation cause an unbalanced
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development in vivo. Young Cha, PhD ; Afshin Beheshti, PhD ; SungBum Cho, PhD ; Michael Peluso, B.S ;
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Philip Hahnfeldt, PhD ; Lynn Hlatky, PhD ; Dohoon Kim, PhD ; and Dohoon KIM Mclean Hospital, Harvard
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Medical School, Belmont, MA ; GRI, Tufts University School of Medicine, Boston, MA ; and GRI, tufts
university school of medicine, Boston, MA
3
One major goal of radiation research is to enable the human exploration of space within
acceptable risks from space radiation. The DNA-damaging effects of gamma or variable radiation sources
are well studied with thousands of publications in the literature investigating the mechanisms and
biological outcomes of these effects. Even so, we are left with insufficient understanding of the various
risks based on traditional means of risk assessment. To augment our understanding, this project aims to
determine and predict Relative Biological Effectivenesses (RBEs) of lower doses of HZE (10-50cGy) and
protons (50-100cGy) for the novel endpoint of epigenetic effect, encompassing the Linear Energy Transfer
(LET) range from 44-250 keV/μm, in vivo. We seek to accomplish this by investigating the epigenetic
memory effects of DNA damage to cells exposed to low doses of different radiation types, using irradiated
mouse and human skin cell-derived induced pluripotent stem cells (iPSCs) as a cellular model for in vivo
development. The goal of these experiments is to determine if radiation is able to induce changes in
cellular differentiation and developmental patterns in vivo by imprinting epigenetic memories in the
radiated cells even after DNA repair. Given the established ability of radiations to modulate carcinogenesis
potential through effects on differentiation state, this might prove to be a very practical, high-throughput
and highly sensitive method for extending our knowledge of low dose radiation risks, particularly at earlier
developmental stages.
(PS7-38) Subject-based supportive care VS population-based care: Effects on survival in non-human
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primates. Jiang-Zhou Yu ; Matt Lindeblad ; Alexander Lyubimov ; Erszebet Szilagyi ; Flavia Neri ; Thomas
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Macvittie ; and Amelia Bartholomew , University of Illinois at Chicago, Chicago, IL and University of
Maryland, Baltimore, MD 2
Subject-based supportive care, informed by individual clinical signs and symptoms, and consisting
of blood transfusions (for a platelet count <20,000), nutritional supplementation, IV hydration, and
antibiotic therapy instituted for severe neutropenia (ANC <500/ μl) has been reported to substantially
improve survival following total body irradiation. In a mass casualty situation, individualized, subject-
based therapy may tax available resources; feasibility issues suggest a need for population-based
strategies. In addition to feasibility testing, population-based strategies can provide uniformity within an
animal model. We compared individualized care (n=46) to population-based care (n=48), defined as IV
hydration, administered prophylactically on set days to all animals, and enrofloxacin, administered to all
animals on post-radiation days 5-21 in rhesus macaques exposed to total body radiation via 6 MV linear
accelerator (LINAC) photon radiation source at a dose rate of 80 + 2.5 cGy/min. Regression analysis of
dose curves revealed the estimated radiation doses for LD30/60, LD50/60 and LD70/60 of animals with
individualized care were 683, 744 and 805cGy, respectively with non-individualized care being 561, 662
and 763cGy, respectively. A dose of 720 cGy was an LD25/60 (n=8) in individualized care and LD75/60
(n=8) with non-individualized care (P=0.04), with greatest gains in survival observed during post-radiation
days 10-15. Improved survival rates in individualized care were associated with statistically higher platelet
counts due to whole blood transfusions and higher absolute neutrophil counts during post-radiation days
372 | P a g e
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1
development in vivo. Young Cha, PhD ; Afshin Beheshti, PhD ; SungBum Cho, PhD ; Michael Peluso, B.S ;
2
2
2
3
Philip Hahnfeldt, PhD ; Lynn Hlatky, PhD ; Dohoon Kim, PhD ; and Dohoon KIM Mclean Hospital, Harvard
1
2
Medical School, Belmont, MA ; GRI, Tufts University School of Medicine, Boston, MA ; and GRI, tufts
university school of medicine, Boston, MA
3
One major goal of radiation research is to enable the human exploration of space within
acceptable risks from space radiation. The DNA-damaging effects of gamma or variable radiation sources
are well studied with thousands of publications in the literature investigating the mechanisms and
biological outcomes of these effects. Even so, we are left with insufficient understanding of the various
risks based on traditional means of risk assessment. To augment our understanding, this project aims to
determine and predict Relative Biological Effectivenesses (RBEs) of lower doses of HZE (10-50cGy) and
protons (50-100cGy) for the novel endpoint of epigenetic effect, encompassing the Linear Energy Transfer
(LET) range from 44-250 keV/μm, in vivo. We seek to accomplish this by investigating the epigenetic
memory effects of DNA damage to cells exposed to low doses of different radiation types, using irradiated
mouse and human skin cell-derived induced pluripotent stem cells (iPSCs) as a cellular model for in vivo
development. The goal of these experiments is to determine if radiation is able to induce changes in
cellular differentiation and developmental patterns in vivo by imprinting epigenetic memories in the
radiated cells even after DNA repair. Given the established ability of radiations to modulate carcinogenesis
potential through effects on differentiation state, this might prove to be a very practical, high-throughput
and highly sensitive method for extending our knowledge of low dose radiation risks, particularly at earlier
developmental stages.
(PS7-38) Subject-based supportive care VS population-based care: Effects on survival in non-human
1
1
1
1
1
primates. Jiang-Zhou Yu ; Matt Lindeblad ; Alexander Lyubimov ; Erszebet Szilagyi ; Flavia Neri ; Thomas
2
1
1
Macvittie ; and Amelia Bartholomew , University of Illinois at Chicago, Chicago, IL and University of
Maryland, Baltimore, MD 2
Subject-based supportive care, informed by individual clinical signs and symptoms, and consisting
of blood transfusions (for a platelet count <20,000), nutritional supplementation, IV hydration, and
antibiotic therapy instituted for severe neutropenia (ANC <500/ μl) has been reported to substantially
improve survival following total body irradiation. In a mass casualty situation, individualized, subject-
based therapy may tax available resources; feasibility issues suggest a need for population-based
strategies. In addition to feasibility testing, population-based strategies can provide uniformity within an
animal model. We compared individualized care (n=46) to population-based care (n=48), defined as IV
hydration, administered prophylactically on set days to all animals, and enrofloxacin, administered to all
animals on post-radiation days 5-21 in rhesus macaques exposed to total body radiation via 6 MV linear
accelerator (LINAC) photon radiation source at a dose rate of 80 + 2.5 cGy/min. Regression analysis of
dose curves revealed the estimated radiation doses for LD30/60, LD50/60 and LD70/60 of animals with
individualized care were 683, 744 and 805cGy, respectively with non-individualized care being 561, 662
and 763cGy, respectively. A dose of 720 cGy was an LD25/60 (n=8) in individualized care and LD75/60
(n=8) with non-individualized care (P=0.04), with greatest gains in survival observed during post-radiation
days 10-15. Improved survival rates in individualized care were associated with statistically higher platelet
counts due to whole blood transfusions and higher absolute neutrophil counts during post-radiation days
372 | P a g e
