Page 368 - 2014 Printable Abstract Book
P. 368
cells. One day after IR, most of the microglia in the hippocampus were still active as indicated by the
expression of the activation marker CD68. One week and one month after IR, the microglia showed a
resting, ramified morphology with very few of them expressed CD68. No infiltrating, RFP-labeled
peripheral monocyte-derived microglia were observed in the brain at any above-mentioned time points.
Hence, unlike after other types of brain injury, such as ischemia or trauma, infiltrating monocytes do not
appear to contribute to the inflammatory response after ionizing radiation.
(PS7-27) Predicting the hematological ARS using gene expression changes examined in the peripheral
1
blood of irradiated baboons - a French-German collaboration. Matthias Port, MD ; Francis J. Herodin,
2
2
1
PhD ; Marco Valente, PhD ; and Michael Abend, MD ; Bundeswehr Institute of Radiobiology, Munich,
Germany and Institut de Recherche Biomedicale des Armees, Bretigny-sur-Orge, France
1
2
Based on gene expression changes measured in the peripheral blood within the first 2 days after
irradiation we aimed to predict the later occurring H-ARS severity. Altogether 18 baboons were
irradiated simulating different patterns of partial body irradiation corresponding to an equivalent dose
of 5 Gy. According to changes in blood cell counts they were either suffering from H1-2 (n=4) or H2-3
(n=13). Blood samples taken before irradiation served as H0 (n=17). A two stage study design was
applied. During first stage we screened the whole genome (mRNA microarrays) and examined 667
miRNA species (qRT-PCR) simultaneously using one part of the samples (n=14). Candidate genes should
be forwarded for validation in phase II using the remaining 20 samples and changing the methodology to
qRT-PCR instead of microarrays. Finally, validated genes will be also applied on H1-2 samples from stage
I and examined for their discrimination ability of different H-ARS severity degrees. We herein present
preliminary data on our microarray results only. From about 20,000 genes on average 46% (range: 34-
54%) appeared expressed. From day 1 to day 2 we observed a decline in the number of differentially
regulated genes from 550 to 94 (up-regulated) and 735 to 64 (down-regulated) for H1-2 and from 1,418
to 1,189 and 1,603 to 797 for H2-3. Differential gene expression was defined as a significant (p<0.05)
and > 2-fold difference in gene expression over the unexposed values. Overlapping numbers of
differentially expressed genes among H1-2 and H2-3 were low (91 up- / 169 down-regulated genes)
leaving about 692 up-regulated and 174 down-regulated candidate genes eligible for discriminating H1-2
from H2-3. These genes did show an enrichment regarding biological processes coding for immune
system processes, natural killer cell activation and immune response. During further analysis we
preselected candidate genes being mutually exclusively differentially expressed at H1-2 or H2-3 only.
Changes in radiation induced gene expression preceding the H-ARS - as expected - are coding for
immunological processes and several hundred candidate genes mutually exclusively expressed either on
H1-2 or H2-3 could be identified to validate the study and to develop a prediction model of H-ARS
severity at phase II of our study.
366 | P a g e
expression of the activation marker CD68. One week and one month after IR, the microglia showed a
resting, ramified morphology with very few of them expressed CD68. No infiltrating, RFP-labeled
peripheral monocyte-derived microglia were observed in the brain at any above-mentioned time points.
Hence, unlike after other types of brain injury, such as ischemia or trauma, infiltrating monocytes do not
appear to contribute to the inflammatory response after ionizing radiation.
(PS7-27) Predicting the hematological ARS using gene expression changes examined in the peripheral
1
blood of irradiated baboons - a French-German collaboration. Matthias Port, MD ; Francis J. Herodin,
2
2
1
PhD ; Marco Valente, PhD ; and Michael Abend, MD ; Bundeswehr Institute of Radiobiology, Munich,
Germany and Institut de Recherche Biomedicale des Armees, Bretigny-sur-Orge, France
1
2
Based on gene expression changes measured in the peripheral blood within the first 2 days after
irradiation we aimed to predict the later occurring H-ARS severity. Altogether 18 baboons were
irradiated simulating different patterns of partial body irradiation corresponding to an equivalent dose
of 5 Gy. According to changes in blood cell counts they were either suffering from H1-2 (n=4) or H2-3
(n=13). Blood samples taken before irradiation served as H0 (n=17). A two stage study design was
applied. During first stage we screened the whole genome (mRNA microarrays) and examined 667
miRNA species (qRT-PCR) simultaneously using one part of the samples (n=14). Candidate genes should
be forwarded for validation in phase II using the remaining 20 samples and changing the methodology to
qRT-PCR instead of microarrays. Finally, validated genes will be also applied on H1-2 samples from stage
I and examined for their discrimination ability of different H-ARS severity degrees. We herein present
preliminary data on our microarray results only. From about 20,000 genes on average 46% (range: 34-
54%) appeared expressed. From day 1 to day 2 we observed a decline in the number of differentially
regulated genes from 550 to 94 (up-regulated) and 735 to 64 (down-regulated) for H1-2 and from 1,418
to 1,189 and 1,603 to 797 for H2-3. Differential gene expression was defined as a significant (p<0.05)
and > 2-fold difference in gene expression over the unexposed values. Overlapping numbers of
differentially expressed genes among H1-2 and H2-3 were low (91 up- / 169 down-regulated genes)
leaving about 692 up-regulated and 174 down-regulated candidate genes eligible for discriminating H1-2
from H2-3. These genes did show an enrichment regarding biological processes coding for immune
system processes, natural killer cell activation and immune response. During further analysis we
preselected candidate genes being mutually exclusively differentially expressed at H1-2 or H2-3 only.
Changes in radiation induced gene expression preceding the H-ARS - as expected - are coding for
immunological processes and several hundred candidate genes mutually exclusively expressed either on
H1-2 or H2-3 could be identified to validate the study and to develop a prediction model of H-ARS
severity at phase II of our study.
366 | P a g e
