Page 325 - 2014 Printable Abstract Book
P. 325
PS6 BIODOSIMETRY, MODELS OF ACUTE RADIATION INJURY
(PS6-01) Cytogenetic Damage in the Blood Lymphocytes of Astronauts: Effects of Repeat Long-Duration
1
1
1
2
Space Missions. Kerry George ; Andrew Beitman ; and Francis A. Cucinotta , Wyle Labs, Houston, TX and
UNLV, Las Vegas, NV
2
Human missions on the International Space Station (ISS) are increasing in duration, and several
astronauts have now participated in second ISS increments. It is unclear whether the effects of space
radiation from multiple missions are simply additive. This question potentially confounds the assessment
of the cumulative health risk from radiation exposure. Single space missions of a few months or more on
the ISS can induce measurable increases in the yield of chromosome damage in the blood lymphocytes of
astronauts, and it appears that cytogenetic biodosimetry can be used reliably to estimate equivalent dose
and radiation risk. We have now obtained direct in vivo measurements of chromosome damage in blood
lymphocytes of five astronauts before and after their first and second long-duration space flights.
Chromosome damage was assessed by the fluorescence in situ hybridization technique using three
different chromosome painting probes. All astronauts showed an increase in total exchanges and
translocations after both the first and second flight. Biological radiation dose, measured using either
individual assessment or a population assessment, supports an additive risk model.
(PS6-02) Measurement of increased GI permeability post-irradiation using fluorescent dextran solution
and correlation with LPS plasma levels. Sarah Hoyle; Matthew Brown; Sam Wrench; Greg Tudor; and Cath
Booth, Epistem Ltd, Manchester, United Kingdom
The symptoms of gastrointestinal acute radiation syndrome (GI-ARS) include weight loss,
diarrhea, dehydration and susceptibility to infection, culminating in mortality. There is an initial shortening
of the crypts and villi followed by crypt loss and ulcer development at times co-incident with the onset of
diarrhea (day 4 post irradiation in C57BL/6 mice). The leakage of enteric bacteria into the bloodstream
due to loss of barrier function is a major cause of mortality. Therapies that improve such barrier function
are therefore likely to prolong survival times post-irradiation. The purpose of this study was firstly to
assess epithelial barrier function at various time points following GI-ARS doses of total-body x-irradiation
(300kVp). C57BL/6 mice (10-12 weeks) were administered oral fluorescent dextran (FD) solution 5hr prior
to euthanasia. As may be expected, time-dependent increases in plasma fluorescence levels were
observed following 12 and 13Gy x-irradiation, peaking at day 4. Following 12Gy there was a slight recovery
at day 6, likely to reflect early crypt regeneration, but this was less evident following 13Gy. In order to
correlate this increased permeability with infection, the appearance of Lipopolysaccharide (LPS) in both
plasma and other tissue was evaluated. LPS is an endotoxin on the outer cell wall of gram-negative
bacteria; release of LPS upon destruction of bacteria produces a strong immune response. Consistent with
increased GI permeability and therefore bacterial translocation, LPS was detected in the plasma of
irradiated mice from day 4. Assessment of tissue lysates demonstrated increased LPS presence in non-
intestinal tissues within 4-6 days, which is characteristic of increased GI permeability and reduced immune
function. Clearly plasma FD and LPS are ready biomarkers of advanced GI-ARS. Further studies to
characterize the radiation dose/time relationship of increased systemic LPS and extent of barrier loss are
underway, including assessment of the effects of antibiotics and partial bone marrow protection on
radiation-induced GI bacterial translocation. These techniques could be utilized to identify potential
323 | P a g e
(PS6-01) Cytogenetic Damage in the Blood Lymphocytes of Astronauts: Effects of Repeat Long-Duration
1
1
1
2
Space Missions. Kerry George ; Andrew Beitman ; and Francis A. Cucinotta , Wyle Labs, Houston, TX and
UNLV, Las Vegas, NV
2
Human missions on the International Space Station (ISS) are increasing in duration, and several
astronauts have now participated in second ISS increments. It is unclear whether the effects of space
radiation from multiple missions are simply additive. This question potentially confounds the assessment
of the cumulative health risk from radiation exposure. Single space missions of a few months or more on
the ISS can induce measurable increases in the yield of chromosome damage in the blood lymphocytes of
astronauts, and it appears that cytogenetic biodosimetry can be used reliably to estimate equivalent dose
and radiation risk. We have now obtained direct in vivo measurements of chromosome damage in blood
lymphocytes of five astronauts before and after their first and second long-duration space flights.
Chromosome damage was assessed by the fluorescence in situ hybridization technique using three
different chromosome painting probes. All astronauts showed an increase in total exchanges and
translocations after both the first and second flight. Biological radiation dose, measured using either
individual assessment or a population assessment, supports an additive risk model.
(PS6-02) Measurement of increased GI permeability post-irradiation using fluorescent dextran solution
and correlation with LPS plasma levels. Sarah Hoyle; Matthew Brown; Sam Wrench; Greg Tudor; and Cath
Booth, Epistem Ltd, Manchester, United Kingdom
The symptoms of gastrointestinal acute radiation syndrome (GI-ARS) include weight loss,
diarrhea, dehydration and susceptibility to infection, culminating in mortality. There is an initial shortening
of the crypts and villi followed by crypt loss and ulcer development at times co-incident with the onset of
diarrhea (day 4 post irradiation in C57BL/6 mice). The leakage of enteric bacteria into the bloodstream
due to loss of barrier function is a major cause of mortality. Therapies that improve such barrier function
are therefore likely to prolong survival times post-irradiation. The purpose of this study was firstly to
assess epithelial barrier function at various time points following GI-ARS doses of total-body x-irradiation
(300kVp). C57BL/6 mice (10-12 weeks) were administered oral fluorescent dextran (FD) solution 5hr prior
to euthanasia. As may be expected, time-dependent increases in plasma fluorescence levels were
observed following 12 and 13Gy x-irradiation, peaking at day 4. Following 12Gy there was a slight recovery
at day 6, likely to reflect early crypt regeneration, but this was less evident following 13Gy. In order to
correlate this increased permeability with infection, the appearance of Lipopolysaccharide (LPS) in both
plasma and other tissue was evaluated. LPS is an endotoxin on the outer cell wall of gram-negative
bacteria; release of LPS upon destruction of bacteria produces a strong immune response. Consistent with
increased GI permeability and therefore bacterial translocation, LPS was detected in the plasma of
irradiated mice from day 4. Assessment of tissue lysates demonstrated increased LPS presence in non-
intestinal tissues within 4-6 days, which is characteristic of increased GI permeability and reduced immune
function. Clearly plasma FD and LPS are ready biomarkers of advanced GI-ARS. Further studies to
characterize the radiation dose/time relationship of increased systemic LPS and extent of barrier loss are
underway, including assessment of the effects of antibiotics and partial bone marrow protection on
radiation-induced GI bacterial translocation. These techniques could be utilized to identify potential
323 | P a g e
