Page 175 - 2014 Printable Abstract Book
P. 175
studies, Neupogen® (10 μg/kg) was administered beginning 1 day post-TBI and continued daily until
neutrophil counts were ≥2,000 /μL for two con-secutive days along with a full medical supportive care.
Blood biosampling was performed prior to and after irradiation for hematological and serum protein
profile analyses. In addition, ARS severity levels in the NHPs were scored using a METREPOL-like scoring
system and prodromal signs and symptoms will be presented. These research findings contribute to
bridging a diagnostic gap to provide current capabilities to rapidly and effectively identify and assess
radiation exposure shortly after a radiation event. Research is supported by Inter-Agency Agreement
between AFRRI and the Biomedical Advanced Research and Development Authority (BARDA) (awarded to
NIO).
(PS2-68) Novel synthetic (S, S) and (R, R) -secoisolariciresinol diglucosides (SDGs) protect naked plasmid
and genomic DNA from gamma radiation damage. Melpo Christofidou-Solomidou, PhD, University of
Pennsylvania, Philadelphia, PA
Background: Secoisolariciresinol diglucoside (SDG) is the major lignan in wholegrain flaxseed.
However extraction methods are complex and are associated with low yield and high costs. Using a novel
synthetic pathway, our group succeeded in chemically synthesizing SDG (S, S and R, R enantiomers) which
faithfully recapitulate the properties of their natural counterparts, possessing strong antioxidant and free
radical scavenging properties. The present study further extends initial findings, by investigating now the
DNA-radioprotective properties of the synthetic SDG enantiomers as they compare to the commercial
SDG. Methods: DNA radioprotection was assessed by cell-free systems such as a) plasmid relaxation assay
by determining the extent of the super coiled (SC) converted to open coiled (OC) plasmid DNA (pBR322)
following exposure of the plasmid to γ-radiation (IR) and b) by determining the extent of genomic DNA
fragmentation. Results: Exposure of plasmid DNA to 25 Gy IR resulted in decreased SC form and increased
OC form, indicating radiation-induced DNA damage. Synthetic SDG (S, S) and SDG (R, R), and commercial
SDG at concentrations of 25-250 µM significantly and equipotently reduced the radiation-induced SC to
OC conversion dose-dependently. Additionally, while exposure of calf thymus DNA to 50 Gy IR resulted in
DNA fragments of low molecular weight (<6,000 bps). This was prevented dose-dependently by all SDG
(synthetic and natural) at concentrations as low as 0.5 µM. Conclusion: These results demonstrate for the
first time that synthetic SDG (S, S) and SDG (R, R) isomers and the commercial SDG possess DNA-
radioprotective properties. Such properties along with their antioxidant and free radical scavenging
activity reported earlier, make SDG a promising candidate for radioprotection for normal tissue damage
resulting from radiation therapy for cancer treatment accidental radiation exposure.
(PS2-69) A purified low-antioxidant diet can mitigate the late effects of radiation to the lung and kidney
3
2;1
1
1
in rats. Brian L. Fish ; Eric P. Cohen ; Jessica B. Flowers ; Meetha Medhora ; and John E. Moulder, 1
1
2
Medical College of Wisconsin, Milwaukee, WI ; Zablocki VAMC, Milwaukee, WI ; and Teklad Diets, Harlan
3
Laboratories, Madison, WI
Introduction: It has been shown that age, gender, size, strain and species all affect the
radiosensitivity of late responding normal tissues. Changes in normal lab animal diets also have an effect
on organ radiosensitivity. Many different base diets are used in animal research. We have observed
changes in radiosensitivity when different diets are used. We have also seen differences depending on
173 | P a g e
neutrophil counts were ≥2,000 /μL for two con-secutive days along with a full medical supportive care.
Blood biosampling was performed prior to and after irradiation for hematological and serum protein
profile analyses. In addition, ARS severity levels in the NHPs were scored using a METREPOL-like scoring
system and prodromal signs and symptoms will be presented. These research findings contribute to
bridging a diagnostic gap to provide current capabilities to rapidly and effectively identify and assess
radiation exposure shortly after a radiation event. Research is supported by Inter-Agency Agreement
between AFRRI and the Biomedical Advanced Research and Development Authority (BARDA) (awarded to
NIO).
(PS2-68) Novel synthetic (S, S) and (R, R) -secoisolariciresinol diglucosides (SDGs) protect naked plasmid
and genomic DNA from gamma radiation damage. Melpo Christofidou-Solomidou, PhD, University of
Pennsylvania, Philadelphia, PA
Background: Secoisolariciresinol diglucoside (SDG) is the major lignan in wholegrain flaxseed.
However extraction methods are complex and are associated with low yield and high costs. Using a novel
synthetic pathway, our group succeeded in chemically synthesizing SDG (S, S and R, R enantiomers) which
faithfully recapitulate the properties of their natural counterparts, possessing strong antioxidant and free
radical scavenging properties. The present study further extends initial findings, by investigating now the
DNA-radioprotective properties of the synthetic SDG enantiomers as they compare to the commercial
SDG. Methods: DNA radioprotection was assessed by cell-free systems such as a) plasmid relaxation assay
by determining the extent of the super coiled (SC) converted to open coiled (OC) plasmid DNA (pBR322)
following exposure of the plasmid to γ-radiation (IR) and b) by determining the extent of genomic DNA
fragmentation. Results: Exposure of plasmid DNA to 25 Gy IR resulted in decreased SC form and increased
OC form, indicating radiation-induced DNA damage. Synthetic SDG (S, S) and SDG (R, R), and commercial
SDG at concentrations of 25-250 µM significantly and equipotently reduced the radiation-induced SC to
OC conversion dose-dependently. Additionally, while exposure of calf thymus DNA to 50 Gy IR resulted in
DNA fragments of low molecular weight (<6,000 bps). This was prevented dose-dependently by all SDG
(synthetic and natural) at concentrations as low as 0.5 µM. Conclusion: These results demonstrate for the
first time that synthetic SDG (S, S) and SDG (R, R) isomers and the commercial SDG possess DNA-
radioprotective properties. Such properties along with their antioxidant and free radical scavenging
activity reported earlier, make SDG a promising candidate for radioprotection for normal tissue damage
resulting from radiation therapy for cancer treatment accidental radiation exposure.
(PS2-69) A purified low-antioxidant diet can mitigate the late effects of radiation to the lung and kidney
3
2;1
1
1
in rats. Brian L. Fish ; Eric P. Cohen ; Jessica B. Flowers ; Meetha Medhora ; and John E. Moulder, 1
1
2
Medical College of Wisconsin, Milwaukee, WI ; Zablocki VAMC, Milwaukee, WI ; and Teklad Diets, Harlan
3
Laboratories, Madison, WI
Introduction: It has been shown that age, gender, size, strain and species all affect the
radiosensitivity of late responding normal tissues. Changes in normal lab animal diets also have an effect
on organ radiosensitivity. Many different base diets are used in animal research. We have observed
changes in radiosensitivity when different diets are used. We have also seen differences depending on
173 | P a g e
