Page 192 - 2014 Printable Abstract Book
P. 192
(PS3-04) Evidence for significant and gene-dependent heritability of transcriptional responses to
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ionising radiation. Sylwia Kabacik, MSc ; Paul Finnon, MSc ; Claudine Raffy, MSc ; Jaakko Kaprio,
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PhD ;Simon Bouffler, PhD ; and Christophe Badie, PhD; Public Health England, Didcot, United Kingdom ,
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Biological Analytical Development Laboratory, VIRBAC, Carros Cedex, France , and Department of Public
Health, University of Helsinki, Helsinki, Finland
3
Humans are exposed to ionising radiation (IR) through the natural environment, medical practices
and industrial applications. There is a natural variability in transcriptional response to IR between
individuals, which may reflect individual sensitivity and cancer susceptibility (Kabacik 2011). Existence of
genetic disorders like Ataxia-Telangiectasia and Gorlin syndrome supports the hypothesis that genetic
factors contribute to differences in human sensitivity to IR exposure and affect individual cancer risk but
health protection policies usually do not take into account the contribution of genetics when assessing
health risks. Twin studies provide a powerful approach to measure the contribution of genetic and
environmental factors to observed human variation. In a previous twin study we showed that variation in
human cellular responses to IR is heritable with significant genetic contribution (Finnon 2008). Here, we
performed a targeted investigation of selected genes involved in different pathways (DNA repair,
apoptosis, cell cycle regulation and stress response) aiming to quantitatively assess the genetic and
environmental contribution to individual transcriptional response to IR. We measured the expression of
nine radiation-responsive genes in stimulated T-lymphocytes before and 2 hours after irradiation with a
2 Gy dose of X-ray in 16 monozygotic and 38 dizygotic twin pairs as well as in 38 unrelated healthy donors.
The data analysis revealed that intra-pair correlation in transcriptional response to IR increased with
genetic relatedness suggesting influence of genetic factors. We estimated genetic and environmental
effects on transcriptional response by fitting our data to structural equation models described in Finnon
et al (Finnon 2008). Expression of four out of nine genes did not meet assumption for twin model hinting
polygenetic effects. For five genes which fitted twin models, the genetic factors explained between 59
and 74 % of the variation in the control samples and between 61 and 82 % in the irradiated samples
indicating that transcriptional response to IR has a highly significant genetic component which differed
between individual genes.
(PS3-05) Comparisons between model predictions and spectral measurements of charged and neutral
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particles on the Martian surface. Myung-Hee Y. Kim, Ph.D , Francis A. Cucinotta, PhD ; Cary Zeitlin, PhD ;
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Donald M. Hassler, PhD ; Bent Ehresmann, PhD ; Scot C.R. Rafkin, PhD ; Robert F. Wimmer-
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Schweingruber, PhD ; Stephan Böttcher, PhD ; Eckart Böhm, PhD ; Jingnan Guo, PhD ; Jan Köhler, PhD ;
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Cesar Martin, PhD ; Guenther Reitz, PhD ; and Arik Posner, PhD USRA/NASA JSC, Houston, TX ; University
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of Nevada Las Vegas, Las Vegas, NV ; Southwest Research Institute, Durham, NH ; Southwest Research
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Institute, Boulder, CO ; Christian Albrechts University, Kiel, Germany ; German Aerospace Center (DLR),
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Cologne, Germany ; and NASA Headquarters, Washington, DC
Detailed measurements of the energetic particle radiation environment on the surface of Mars
have been made by the Radiation Assessment Detector (RAD) on the Curiosity rover since August 2012.
RAD is a particle detector that measures the energy spectrum of charged particles (10 to ~200 MeV/u)
and high energy neutrons (~8 to 200 MeV). Although the data obtained on the surface of Mars for 300
sols are limited in the narrow energy spectra, the simulation results using the Badhwar-O’Neill galactic
cosmic ray (GCR) environment model and the high-charge and energy transport (HZETRN) code are
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ionising radiation. Sylwia Kabacik, MSc ; Paul Finnon, MSc ; Claudine Raffy, MSc ; Jaakko Kaprio,
3
1
1
1
PhD ;Simon Bouffler, PhD ; and Christophe Badie, PhD; Public Health England, Didcot, United Kingdom ,
2
Biological Analytical Development Laboratory, VIRBAC, Carros Cedex, France , and Department of Public
Health, University of Helsinki, Helsinki, Finland
3
Humans are exposed to ionising radiation (IR) through the natural environment, medical practices
and industrial applications. There is a natural variability in transcriptional response to IR between
individuals, which may reflect individual sensitivity and cancer susceptibility (Kabacik 2011). Existence of
genetic disorders like Ataxia-Telangiectasia and Gorlin syndrome supports the hypothesis that genetic
factors contribute to differences in human sensitivity to IR exposure and affect individual cancer risk but
health protection policies usually do not take into account the contribution of genetics when assessing
health risks. Twin studies provide a powerful approach to measure the contribution of genetic and
environmental factors to observed human variation. In a previous twin study we showed that variation in
human cellular responses to IR is heritable with significant genetic contribution (Finnon 2008). Here, we
performed a targeted investigation of selected genes involved in different pathways (DNA repair,
apoptosis, cell cycle regulation and stress response) aiming to quantitatively assess the genetic and
environmental contribution to individual transcriptional response to IR. We measured the expression of
nine radiation-responsive genes in stimulated T-lymphocytes before and 2 hours after irradiation with a
2 Gy dose of X-ray in 16 monozygotic and 38 dizygotic twin pairs as well as in 38 unrelated healthy donors.
The data analysis revealed that intra-pair correlation in transcriptional response to IR increased with
genetic relatedness suggesting influence of genetic factors. We estimated genetic and environmental
effects on transcriptional response by fitting our data to structural equation models described in Finnon
et al (Finnon 2008). Expression of four out of nine genes did not meet assumption for twin model hinting
polygenetic effects. For five genes which fitted twin models, the genetic factors explained between 59
and 74 % of the variation in the control samples and between 61 and 82 % in the irradiated samples
indicating that transcriptional response to IR has a highly significant genetic component which differed
between individual genes.
(PS3-05) Comparisons between model predictions and spectral measurements of charged and neutral
1
3
2
particles on the Martian surface. Myung-Hee Y. Kim, Ph.D , Francis A. Cucinotta, PhD ; Cary Zeitlin, PhD ;
4
4
4
Donald M. Hassler, PhD ; Bent Ehresmann, PhD ; Scot C.R. Rafkin, PhD ; Robert F. Wimmer-
5
5
5
5
5
Schweingruber, PhD ; Stephan Böttcher, PhD ; Eckart Böhm, PhD ; Jingnan Guo, PhD ; Jan Köhler, PhD ;
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6
5
Cesar Martin, PhD ; Guenther Reitz, PhD ; and Arik Posner, PhD USRA/NASA JSC, Houston, TX ; University
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2
of Nevada Las Vegas, Las Vegas, NV ; Southwest Research Institute, Durham, NH ; Southwest Research
5
4
Institute, Boulder, CO ; Christian Albrechts University, Kiel, Germany ; German Aerospace Center (DLR),
7
6
Cologne, Germany ; and NASA Headquarters, Washington, DC
Detailed measurements of the energetic particle radiation environment on the surface of Mars
have been made by the Radiation Assessment Detector (RAD) on the Curiosity rover since August 2012.
RAD is a particle detector that measures the energy spectrum of charged particles (10 to ~200 MeV/u)
and high energy neutrons (~8 to 200 MeV). Although the data obtained on the surface of Mars for 300
sols are limited in the narrow energy spectra, the simulation results using the Badhwar-O’Neill galactic
cosmic ray (GCR) environment model and the high-charge and energy transport (HZETRN) code are
190 | P a g e
