Page 77 - 2014 Printable Abstract Book
P. 77
(S1904) Does HZE exacerbate neurodegenerative disease? Evidence from preclinical models.
M. Kerry O'Banion, University of Rochester Medical Center, Rochester, NY
An individual’s susceptibility to neurodegenerative diseases is influenced by multiple genetic and
environmental factors. Given the prevalence of such diseases in our aging population, and evidence that
irradiation can provoke degenerative changes, there is concern that astronauts exposed to chronic space
radiation may be at increased risk for common neurodegenerative diseases such as Alzheimer’s (AD) and
Parkinson’s disease (PD). We have begun to test this possibility by irradiating transgenic mouse models of
AD and PD at the NASA Space Radiation Laboratory. We previously reported impaired cognitive
performance and increased amyloid plaque pathology in the APPswe/PS-1dE9 transgenic AD mouse
56
model following exposure to 1 MeV/n Fe particles (Cherry et al. 2012. PLoS One 7:e53275). Details of
this study will be presented, as will recent preliminary data showing increased plaque pathology in a
different AD mouse model after low LET irradiation. Neurodegenerative disorders are characterized by
chronic neuroinflammation and oxidative stress, which can be elicited by modest doses of HZE. These and
other possible mechanistic links between radiation exposure and neurodegeneration will be discussed.
Supported by NASA Grants NNX08BA09G and NNX13AC33G.
S 20 ADAPTIVE RESPONSES: AN ACADEMIC CURIOUSITY OR A CLINICAL ISSUE
In the context of radiation biology the adaptive response can be defined as the ability of cells or organisms
exposed to a very low dose of ionizing radiation to confer enhanced resistance to a subsequent exposure
to a much larger dose of radiation. Recognized almost 30 years ago, this phenomenon has been
investigated extensively. With the development and implementation of very low dose imaging procedures
such as computerized axial tomography to position and monitor tumors undergoing treatment in image
guided radiotherapy protocols, new concerns arise as to the potential for and the consequences of the
development of therapy modifying- adaptive responses. This symposium will address the development
and relevance of these adaptive responses as they affect therapeutic gain for human exposures including
their potential for mitigating both acute and late effects in dose limiting normal tissues and tumors.
(S2001) Low Dose Diagnostic Radiation Does Not Increase Cancer Risk in Cancer Prone Mice.
1
Douglas Boreham ; Nghi Phau ; and Jennifer Lemon, Northern Ontario School of Medicine, Sudbury,
2
3
Canada ; University of Ottawa, Ottawa, Canada ; and McMaster University, Hamilton, Canada
3
1
2
The increased exposure of patients to low dose diagnostic ionizing radiation has created concern that
these procedures will result in greater risk of carcinogenesis. However, there is substantial evidence that
shows in many cases that low dose exposure has the opposite effect. We have investigated whether CT
scans can modify mechanisms associated with carcinogenesis in cancer-prone mice. Cancer was induced
in Trp53+/- mice with an acute high dose whole-body 4 Gy γ-radiation exposure. Four weeks following the
cancer-inducing dose, weekly whole-body CT scans (10 mGy/scan, 75 kVp X-rays) were given for ten
consecutive weeks. Short-term biological responses and subsequent lifetime cancer risk were
investigated. Five days following the last CT scan, there were no detectable differences in the spontaneous
levels of DNA damage in blood cells (reticulocytes). In fact, CT scanned mice had significantly lower
constitutive levels of oxidative DNA damage and cell death (apoptosis) at 9% and 20% respectively,
75 | P a g e
M. Kerry O'Banion, University of Rochester Medical Center, Rochester, NY
An individual’s susceptibility to neurodegenerative diseases is influenced by multiple genetic and
environmental factors. Given the prevalence of such diseases in our aging population, and evidence that
irradiation can provoke degenerative changes, there is concern that astronauts exposed to chronic space
radiation may be at increased risk for common neurodegenerative diseases such as Alzheimer’s (AD) and
Parkinson’s disease (PD). We have begun to test this possibility by irradiating transgenic mouse models of
AD and PD at the NASA Space Radiation Laboratory. We previously reported impaired cognitive
performance and increased amyloid plaque pathology in the APPswe/PS-1dE9 transgenic AD mouse
56
model following exposure to 1 MeV/n Fe particles (Cherry et al. 2012. PLoS One 7:e53275). Details of
this study will be presented, as will recent preliminary data showing increased plaque pathology in a
different AD mouse model after low LET irradiation. Neurodegenerative disorders are characterized by
chronic neuroinflammation and oxidative stress, which can be elicited by modest doses of HZE. These and
other possible mechanistic links between radiation exposure and neurodegeneration will be discussed.
Supported by NASA Grants NNX08BA09G and NNX13AC33G.
S 20 ADAPTIVE RESPONSES: AN ACADEMIC CURIOUSITY OR A CLINICAL ISSUE
In the context of radiation biology the adaptive response can be defined as the ability of cells or organisms
exposed to a very low dose of ionizing radiation to confer enhanced resistance to a subsequent exposure
to a much larger dose of radiation. Recognized almost 30 years ago, this phenomenon has been
investigated extensively. With the development and implementation of very low dose imaging procedures
such as computerized axial tomography to position and monitor tumors undergoing treatment in image
guided radiotherapy protocols, new concerns arise as to the potential for and the consequences of the
development of therapy modifying- adaptive responses. This symposium will address the development
and relevance of these adaptive responses as they affect therapeutic gain for human exposures including
their potential for mitigating both acute and late effects in dose limiting normal tissues and tumors.
(S2001) Low Dose Diagnostic Radiation Does Not Increase Cancer Risk in Cancer Prone Mice.
1
Douglas Boreham ; Nghi Phau ; and Jennifer Lemon, Northern Ontario School of Medicine, Sudbury,
2
3
Canada ; University of Ottawa, Ottawa, Canada ; and McMaster University, Hamilton, Canada
3
1
2
The increased exposure of patients to low dose diagnostic ionizing radiation has created concern that
these procedures will result in greater risk of carcinogenesis. However, there is substantial evidence that
shows in many cases that low dose exposure has the opposite effect. We have investigated whether CT
scans can modify mechanisms associated with carcinogenesis in cancer-prone mice. Cancer was induced
in Trp53+/- mice with an acute high dose whole-body 4 Gy γ-radiation exposure. Four weeks following the
cancer-inducing dose, weekly whole-body CT scans (10 mGy/scan, 75 kVp X-rays) were given for ten
consecutive weeks. Short-term biological responses and subsequent lifetime cancer risk were
investigated. Five days following the last CT scan, there were no detectable differences in the spontaneous
levels of DNA damage in blood cells (reticulocytes). In fact, CT scanned mice had significantly lower
constitutive levels of oxidative DNA damage and cell death (apoptosis) at 9% and 20% respectively,
75 | P a g e
