Page 52 - 2014 Printable Abstract Book
P. 52
(S904) Protein and miRNA analysis using human cardiac samples from the SUBI archives. Mayur V.
2
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1
1
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Bakshi ; Omid Azimzadeh ; Juliane Merl ; Vanja Radulovic ; Tamara Azizova ; Michael J. Atkinson ; Natasa
1
1
1
Anastasov ; Soile Tapio, Helmholtz Centre Munich, Neuherberg, Germany and Southern Urals Biophysic
Institute, Ozyorsk, Russian Federation
2
Chronic low-dose ionizing radiation induces cardiovascular disease in human populations but the
mechanisms are largely unknown. The workers of the Mayak PA plutonium reprocessing plant show
increased risk of ischemic heart disease (IHD). Heart left ventricle samples were collected in autopsy from
exposed workers and unexposed controls. Criteria for inclusion in the study were exposure mainly to
external gamma rays, death following IHD (ICD-9 410-414) and IHD diagnosed during the life time. Criteria
for exclusion included exposure to high or unknown doses of internal plutonium (body burden > 0.5 kBq)
or diagnosis of cancer or severe somatic disease. Formalin-fixed paraffin-embedded (FFPE) samples from
48 individuals were collected from 6, 10, 16 and 16 persons representing dose groups of 0 Gy, less than
0.1 Gy, 0.1 - 0.5 Gy and more than 0.5 Gy, respectively. The microRNA analysis was done using either Low
Density TaqMan Array (384 miRNAs) or TaqMan single assays. In addition, fresh-frozen left ventricle and
coronary artery samples were collected from 25 individuals representing similar dose groups as before,
16 of them overlapping with the FFPE sample donors. A global proteomics analysis was done using
Quadruplex Isotope-Coded Protein Label method from both pooled and individual samples. In the first
analysis all samples from the same dose group were pooled and compared to the pooled control. In the
second analysis the samples from exposed individuals were matched by gender and age to form a group
of three individuals and compared to a pooled control sample. The proteins alterations were considered
significant if the variability was less than 40% and the protein was dysregulated (fold change >1.3 or <
0.77) in at least five out of eight individual groups. The radiation-induced miRNAome and proteome
changes and their interaction network will be discussed.
S10 DEVELOPMENT OF RADIATION BIODOSIMETERS
This symposium will focus on the process of developing biodosimetry tools for use in large-scale
radiological or nuclear incidents. Starting with an introduction describing the US Government’s program
to support advanced development of biodosimetry platforms and assays, the session will then update
validation progress for six government-supported product developers exploiting such diverse
technologies as proteomics, genomics, electron paramagnetic resonance, and lymphocyte cytokinesis-
block micronucleus assays. Augmenting these development efforts are partner biomedical research
organizations that contribute fractionated and total body irradiation models and prompt effects modeling
to enable further validation of developers’ biodosimetry platforms. A description of the animal modeling
work used for biomarker panel discovery and algorithm testing will be presented. Another speaker will
explain how knowledge of the atmospheric dispersion and prompt effects models also enable the
biodosimetry developers. To illustrate the progress achieved to date, two groups will present their most
recent advances toward obtaining FDA clearance for tests designed to provide estimates of absorbed
radiation dose. The first will describe a high-throughput assay measuring gene expression profile changes
to quantitate dose absorption. The second group will present progress on a handheld point-of-care device
scanning protein markers to qualitatively predict clinically relevant threshold dose absorption. Overall,
this session will elucidate the steps involved in developing a biodosimeter, the challenges in obtaining a
robust test and the technical and regulatory hurdles faced by product developers.
50 | P a g e
2
1
1
1
1
1
Bakshi ; Omid Azimzadeh ; Juliane Merl ; Vanja Radulovic ; Tamara Azizova ; Michael J. Atkinson ; Natasa
1
1
1
Anastasov ; Soile Tapio, Helmholtz Centre Munich, Neuherberg, Germany and Southern Urals Biophysic
Institute, Ozyorsk, Russian Federation
2
Chronic low-dose ionizing radiation induces cardiovascular disease in human populations but the
mechanisms are largely unknown. The workers of the Mayak PA plutonium reprocessing plant show
increased risk of ischemic heart disease (IHD). Heart left ventricle samples were collected in autopsy from
exposed workers and unexposed controls. Criteria for inclusion in the study were exposure mainly to
external gamma rays, death following IHD (ICD-9 410-414) and IHD diagnosed during the life time. Criteria
for exclusion included exposure to high or unknown doses of internal plutonium (body burden > 0.5 kBq)
or diagnosis of cancer or severe somatic disease. Formalin-fixed paraffin-embedded (FFPE) samples from
48 individuals were collected from 6, 10, 16 and 16 persons representing dose groups of 0 Gy, less than
0.1 Gy, 0.1 - 0.5 Gy and more than 0.5 Gy, respectively. The microRNA analysis was done using either Low
Density TaqMan Array (384 miRNAs) or TaqMan single assays. In addition, fresh-frozen left ventricle and
coronary artery samples were collected from 25 individuals representing similar dose groups as before,
16 of them overlapping with the FFPE sample donors. A global proteomics analysis was done using
Quadruplex Isotope-Coded Protein Label method from both pooled and individual samples. In the first
analysis all samples from the same dose group were pooled and compared to the pooled control. In the
second analysis the samples from exposed individuals were matched by gender and age to form a group
of three individuals and compared to a pooled control sample. The proteins alterations were considered
significant if the variability was less than 40% and the protein was dysregulated (fold change >1.3 or <
0.77) in at least five out of eight individual groups. The radiation-induced miRNAome and proteome
changes and their interaction network will be discussed.
S10 DEVELOPMENT OF RADIATION BIODOSIMETERS
This symposium will focus on the process of developing biodosimetry tools for use in large-scale
radiological or nuclear incidents. Starting with an introduction describing the US Government’s program
to support advanced development of biodosimetry platforms and assays, the session will then update
validation progress for six government-supported product developers exploiting such diverse
technologies as proteomics, genomics, electron paramagnetic resonance, and lymphocyte cytokinesis-
block micronucleus assays. Augmenting these development efforts are partner biomedical research
organizations that contribute fractionated and total body irradiation models and prompt effects modeling
to enable further validation of developers’ biodosimetry platforms. A description of the animal modeling
work used for biomarker panel discovery and algorithm testing will be presented. Another speaker will
explain how knowledge of the atmospheric dispersion and prompt effects models also enable the
biodosimetry developers. To illustrate the progress achieved to date, two groups will present their most
recent advances toward obtaining FDA clearance for tests designed to provide estimates of absorbed
radiation dose. The first will describe a high-throughput assay measuring gene expression profile changes
to quantitate dose absorption. The second group will present progress on a handheld point-of-care device
scanning protein markers to qualitatively predict clinically relevant threshold dose absorption. Overall,
this session will elucidate the steps involved in developing a biodosimeter, the challenges in obtaining a
robust test and the technical and regulatory hurdles faced by product developers.
50 | P a g e
