Page 349 - 2014 Printable Abstract Book
P. 349
capabilities allow for immediate irradiation and usage of blood. To prevent Transfusion Associated Graft
vs. Host Disease (TA-GVHD) blood is irradiated to 25 Gy mid-line value (Moroff and Luban 1997). Herein
we show results of lymphocyte depletion and platelet activation assays of our transfusion blood.
1
1
(PS6-42) The radiobiological response of the mouse intestine. Greg Tudor, B.Sc. ; Julie Tudor, B.Sc. ;
1
1
2
Thomas MacVittie, Ph.D ; and Catherine Booth, PhD ; Epistem Ltd, Manchester, United Kingdom and
2
University of Maryland, Baltimore, MD
The NIAID sponsored Medical Countermeasures against Radiological Threats (MCART) consortium
is charged with developing medical countermeasures to treat the key sequelae of the acute and delayed
effects of radiation syndrome. The first effect to manifest post irradiation is gastrointestinal acute
radiation syndrome (GI-ARS). In order to define the mechanism of action of potential counter-measures
to GI-ARS it is crucial to have a complete understanding of the baseline response of the intestine to
radiation. A large study was therefore recently undertaken to generate probably the most comprehensive
data set ever produced of the radiobiological response of the adult mouse intestine. 10-12 week old
C57Bl/6 mice were exposed to total body irradiation (300 kV X-ray, 10mA, with additional filtration to give
a radiation quality of 2.3 mm Cu HVL) at 6-15Gy in 1Gy increments at an exposure rate of 0.812Gy/minute.
This dose range covers both the mid H-ARS (haematological) to GI-ARS radiation exposure levels. Groups
of five animals were euthanised daily over 6 days and the different regions of the intestine (duodenum,
jejunum, upper and lower ileum) individually analysed for effects on crypt number and size, and compared
to unirradiated controls. In total 1260 intestinal regions were analysed and 10 intestinal cross sections per
region evaluated. Complete blood counts were performed and plasma collected for citrulline
measurement (previously reported). Intestinal regions were fixed, paraffin embedded, sectioned and H&E
stained for histological analysis. The extent and duration of crypt shrinkage, loss and initiation of recovery
was recorded. When compared to starting crypt number there was a remarkable consistency of response
between intestinal regions, although surprisingly the jejunum was slightly more radio-resistant than the
other regions. The dramatic changes in maximal crypt width in the surviving regenerating crypts directly
correlated with the extent of loss of adjacent crypts, and underscores the need to monitor size changes
when quantifying crypt numbers in histological cross sections. The detailed response over time, in effect
a movie, was therefore generated for each dose of irradiation in each intestinal region and provides a
unique baseline dataset. Supported by NIAID contract HHSN272201000046C.
(PS6-43) Oxidative damage and inflammatory response in mice exposed to whole-body gamma
irradiation: Alterations in the radioprotective effects of a dietary supplement. Jennifer A. Lemon, PhD ;
1
1
2
1
Kathleen Monster, BSc ; C. David Rollo, PhD ; and Douglas R. Boreham, PhD , McMaster University,
2
Hamilton, Canada and Northern Ontario School of Medicine, Sudbury, Canada
1
Previous studies indicate a dietary supplement originally designed to off-set 5 key mechanisms
associated with aging (oxidative damage, inflammation, impaired glucose metabolism, mitochondrial
dysfunction and membrane deterioration), has significant radioprotective effects on hematopoietic
tissue. The supplement appears to provide protection by ameliorating oxidative stress at the time of
irradiation, resulting in reductions in chromosomal aberrations, oxidative DNA damage and apoptosis in
bone marrow and peripheral blood cells. Experimental animals are normally fed the dietary supplement
347 | P a g e
vs. Host Disease (TA-GVHD) blood is irradiated to 25 Gy mid-line value (Moroff and Luban 1997). Herein
we show results of lymphocyte depletion and platelet activation assays of our transfusion blood.
1
1
(PS6-42) The radiobiological response of the mouse intestine. Greg Tudor, B.Sc. ; Julie Tudor, B.Sc. ;
1
1
2
Thomas MacVittie, Ph.D ; and Catherine Booth, PhD ; Epistem Ltd, Manchester, United Kingdom and
2
University of Maryland, Baltimore, MD
The NIAID sponsored Medical Countermeasures against Radiological Threats (MCART) consortium
is charged with developing medical countermeasures to treat the key sequelae of the acute and delayed
effects of radiation syndrome. The first effect to manifest post irradiation is gastrointestinal acute
radiation syndrome (GI-ARS). In order to define the mechanism of action of potential counter-measures
to GI-ARS it is crucial to have a complete understanding of the baseline response of the intestine to
radiation. A large study was therefore recently undertaken to generate probably the most comprehensive
data set ever produced of the radiobiological response of the adult mouse intestine. 10-12 week old
C57Bl/6 mice were exposed to total body irradiation (300 kV X-ray, 10mA, with additional filtration to give
a radiation quality of 2.3 mm Cu HVL) at 6-15Gy in 1Gy increments at an exposure rate of 0.812Gy/minute.
This dose range covers both the mid H-ARS (haematological) to GI-ARS radiation exposure levels. Groups
of five animals were euthanised daily over 6 days and the different regions of the intestine (duodenum,
jejunum, upper and lower ileum) individually analysed for effects on crypt number and size, and compared
to unirradiated controls. In total 1260 intestinal regions were analysed and 10 intestinal cross sections per
region evaluated. Complete blood counts were performed and plasma collected for citrulline
measurement (previously reported). Intestinal regions were fixed, paraffin embedded, sectioned and H&E
stained for histological analysis. The extent and duration of crypt shrinkage, loss and initiation of recovery
was recorded. When compared to starting crypt number there was a remarkable consistency of response
between intestinal regions, although surprisingly the jejunum was slightly more radio-resistant than the
other regions. The dramatic changes in maximal crypt width in the surviving regenerating crypts directly
correlated with the extent of loss of adjacent crypts, and underscores the need to monitor size changes
when quantifying crypt numbers in histological cross sections. The detailed response over time, in effect
a movie, was therefore generated for each dose of irradiation in each intestinal region and provides a
unique baseline dataset. Supported by NIAID contract HHSN272201000046C.
(PS6-43) Oxidative damage and inflammatory response in mice exposed to whole-body gamma
irradiation: Alterations in the radioprotective effects of a dietary supplement. Jennifer A. Lemon, PhD ;
1
1
2
1
Kathleen Monster, BSc ; C. David Rollo, PhD ; and Douglas R. Boreham, PhD , McMaster University,
2
Hamilton, Canada and Northern Ontario School of Medicine, Sudbury, Canada
1
Previous studies indicate a dietary supplement originally designed to off-set 5 key mechanisms
associated with aging (oxidative damage, inflammation, impaired glucose metabolism, mitochondrial
dysfunction and membrane deterioration), has significant radioprotective effects on hematopoietic
tissue. The supplement appears to provide protection by ameliorating oxidative stress at the time of
irradiation, resulting in reductions in chromosomal aberrations, oxidative DNA damage and apoptosis in
bone marrow and peripheral blood cells. Experimental animals are normally fed the dietary supplement
347 | P a g e
