Page 200 - 2014 Printable Abstract Book
P. 200
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(PS3-17) Cellular and molecular alterations in the heart in response to Fe and protons. Marjan
1
1
1
1
1
Boerma ; Igor Koturbash ; Vijayalakshmi Sridharan ; Isabelle Racine-Miousse ; Martin Hauer-Jensen ; and
2
1
Gregory A. Nelson University of Arkansas for Medical Sciences, Little Rock, AR and Loma Linda University,
Loma Linda, CA
2
Background: Recent evidence suggests that the heart may be injured by ionizing radiation at lower
doses than was previously thought. This raises concern about risks of cardiovascular disease from
radiation exposure during space travel. This study used a mouse model to characterize short-term and
long-term cellular and molecular changes in the heart in response to whole-body exposure to Fe or
56
56
protons. Methods: Male C57BL/6 mice at 10 weeks of age were exposed to 50 cGy of Fe, 10 cGy of
protons, or sham-irradiation. Hearts were obtained at 7 days and 90 days post-irradiation and snap-frozen
for analysis of markers of cell death, cardiac remodeling, inflammatory infiltration, and DNA methylation.
56
Results: Cellular autophagy was observed at 7 days after exposure to Fe and protons. At both time
points, increased levels of CD2 and CD68 indicated increased inflammatory infiltration in hearts of animals
exposed to Fe, but not protons. These cellular changes coincided with a small but significant increase in
56
DNA methylation, most pronounced in the 56 Fe group, at the 90 day time point.
Conclusions: These results indicate that low doses of high-LET radiation may cause adverse remodeling,
inflammation, and epigenetic changes in the heart. Further investigation is required to identify
mechanisms by which high-LET radiation modifies cardiac function and structure.
(PS3-19) Micronucleus formation in human keratinocytes is dependent on radiation quality and tissue
architecture. Claudia Wiese, PhD; Brandon J. Mannion; Stanley G. Leung; Sol Moon; Amy Kronenberg; and
Antoine M. Snijders, Lawrence Berkeley National Laboratory, Berkeley, CA
The cytokinesis-block micronucleus (MN) assay was used to assess the genotoxicity of low doses
of different types of space radiation. Normal human primary keratinocytes and immortalized
keratinocytes grown in 2D monolayers were each exposed to graded doses of 0.3 or 1.0 GeV/n silicon ions
or similar energies of iron ions. The frequencies of induced MN were determined and compared to γ-ray
data. RBEmax values ranged from 2.0 to 3.9 for primary keratinocytes and from 2.4 to 6.3 for immortalized
keratinocytes. At low radiation doses ≤ 0.4 Gy, 0.3 GeV/n iron ions were the most effective at inducing
MN in normal keratinocytes. An “over-kill effect” was observed for 0.3 GeV/n iron ions at higher doses,
wherein 1.0 GeV/n iron ions were most efficient in inducing MN. In immortalized keratinocytes, 0.3 GeV/n
iron ions produced MN with greater frequency than 1.0 GeV/n iron ions, except at the highest dose tested.
MN formation was higher in immortalized keratinocytes than in normal keratinocytes for all doses and
radiation qualities investigated. MN induction was also assessed in human keratinocytes cultured in 3D to
simulate the complex architecture of the human skin. RBE values for MN formation in 3D were reduced
for normal keratinocytes exposed to iron ions, but were elevated for immortalized keratinocytes. Overall,
MN induction was significantly lower in keratinocytes cultured in 3D than in 2D. We suggest that the
mechanisms of the early DNA damage response associated with high LET heavy ion exposures are
dependent on tissue architecture and the state of cellular immortalization. These factors should be
198 | P a g e
(PS3-17) Cellular and molecular alterations in the heart in response to Fe and protons. Marjan
1
1
1
1
1
Boerma ; Igor Koturbash ; Vijayalakshmi Sridharan ; Isabelle Racine-Miousse ; Martin Hauer-Jensen ; and
2
1
Gregory A. Nelson University of Arkansas for Medical Sciences, Little Rock, AR and Loma Linda University,
Loma Linda, CA
2
Background: Recent evidence suggests that the heart may be injured by ionizing radiation at lower
doses than was previously thought. This raises concern about risks of cardiovascular disease from
radiation exposure during space travel. This study used a mouse model to characterize short-term and
long-term cellular and molecular changes in the heart in response to whole-body exposure to Fe or
56
56
protons. Methods: Male C57BL/6 mice at 10 weeks of age were exposed to 50 cGy of Fe, 10 cGy of
protons, or sham-irradiation. Hearts were obtained at 7 days and 90 days post-irradiation and snap-frozen
for analysis of markers of cell death, cardiac remodeling, inflammatory infiltration, and DNA methylation.
56
Results: Cellular autophagy was observed at 7 days after exposure to Fe and protons. At both time
points, increased levels of CD2 and CD68 indicated increased inflammatory infiltration in hearts of animals
exposed to Fe, but not protons. These cellular changes coincided with a small but significant increase in
56
DNA methylation, most pronounced in the 56 Fe group, at the 90 day time point.
Conclusions: These results indicate that low doses of high-LET radiation may cause adverse remodeling,
inflammation, and epigenetic changes in the heart. Further investigation is required to identify
mechanisms by which high-LET radiation modifies cardiac function and structure.
(PS3-19) Micronucleus formation in human keratinocytes is dependent on radiation quality and tissue
architecture. Claudia Wiese, PhD; Brandon J. Mannion; Stanley G. Leung; Sol Moon; Amy Kronenberg; and
Antoine M. Snijders, Lawrence Berkeley National Laboratory, Berkeley, CA
The cytokinesis-block micronucleus (MN) assay was used to assess the genotoxicity of low doses
of different types of space radiation. Normal human primary keratinocytes and immortalized
keratinocytes grown in 2D monolayers were each exposed to graded doses of 0.3 or 1.0 GeV/n silicon ions
or similar energies of iron ions. The frequencies of induced MN were determined and compared to γ-ray
data. RBEmax values ranged from 2.0 to 3.9 for primary keratinocytes and from 2.4 to 6.3 for immortalized
keratinocytes. At low radiation doses ≤ 0.4 Gy, 0.3 GeV/n iron ions were the most effective at inducing
MN in normal keratinocytes. An “over-kill effect” was observed for 0.3 GeV/n iron ions at higher doses,
wherein 1.0 GeV/n iron ions were most efficient in inducing MN. In immortalized keratinocytes, 0.3 GeV/n
iron ions produced MN with greater frequency than 1.0 GeV/n iron ions, except at the highest dose tested.
MN formation was higher in immortalized keratinocytes than in normal keratinocytes for all doses and
radiation qualities investigated. MN induction was also assessed in human keratinocytes cultured in 3D to
simulate the complex architecture of the human skin. RBE values for MN formation in 3D were reduced
for normal keratinocytes exposed to iron ions, but were elevated for immortalized keratinocytes. Overall,
MN induction was significantly lower in keratinocytes cultured in 3D than in 2D. We suggest that the
mechanisms of the early DNA damage response associated with high LET heavy ion exposures are
dependent on tissue architecture and the state of cellular immortalization. These factors should be
198 | P a g e
