Page 191 - 2014 Printable Abstract Book
P. 191
mice were euthanized and skin sample were harvested. Changes in expression of genes involved in
oxidative stress, and ECM were examined. Many genes responsible for regulating production and
metabolism of reactive oxygen species (ROS) and ECM remodeling were significantly (p<0.05) altered. To
characterize the metabolic effects of space flight in the skin of mice, global biochemical profiles were
compared in space-flown mice and AEM skin. Of 332 named biochemicals, 19 biochemicals differed
significantly (p<0.05) between space flight skin samples and AEM ground controls. Collectively, the data
demonstrated that space flight condition leads to a shift in homeostasis as the consequence of up/down-
regulation in cellular antioxidants, increases in production of ROS, and tissue remodeling through altered
expression of genes involved in the accumulation and degradation of ECM components. Space flight also
alters several aspects of mouse skin metabolism (redox imbalance). This indicates that astronauts may be
at increased risk for pathophysiologic damage or carcinogenesis in the dermal-tissue.
(PS3-03) Transcriptome profiling and differential gene set enrichment analysis in 3-D epithelial models
following exposure to gamma-ray and HZE particle radiation. Zarana S. Patel, Yared H. Kidane, and Janice
L. Huff, NASA Johnson Space Center / USRA, Houston, TX
Reducing uncertainties in current risk models for assessment of space radiation-induced cancers
requires new knowledge on the fundamental differences in biological responses (the so-called radiation
quality effects) triggered by galactic cosmic rays versus low-LET radiation associated with Earth-based
exposures. In order to characterize radiation quality effects, we are utilizing novel 3-D organotypic human
tissue models for risk assessment as a format for the study of human cells within a realistic tissue
framework; these models help bridge the gap between 2-D monolayer cultures and animal models for risk
extrapolation to humans. To gain insight into potential differences in the biological response of cells to
HZE particle radiation compared to low-LET gamma-rays, we performed global gene expression profiling
of esophageal epithelial cells grown in 3-D cultures at 72 hours following exposure to equitoxic doses of
137Cs gamma-rays or 48Ti ions (350 MeV/u) using Illumina platform (HT12 Expression Beadchip) arrays.
Functional gene set enrichment analysis (GSEA) was used to identify biological pathway signatures that
were unique to heavy ion particle exposure. We identified 45 statistically significant gene sets at 0.05 q-
value cutoff, including 14 gene sets common to gamma and titanium irradiation, 19 gene sets specific to
gamma-rays, and 12 titanium-specific gene sets. Common gene sets aligned with DNA damage and
immune system and inflammatory cytokine pathway activation. The top gene set enriched for the gamma-
irradiated samples involved KRAS pathway activation, with overall enrichment in genes related to
extracellular matrix regulation. For titanium exposure, the top ranking gene set contained genes whose
expression was increased in TNF-treated cells, with overall enrichment in genes involved in TGF-β and
cytokine pathways. These results suggest that GSEA is a powerful approach for assessing the functional
significance of radiation quality-dependent changes from datasets where the changes are subtle but
broad, and where analysis based on rankings of single gene fold-changes may not reveal important
biological information.
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oxidative stress, and ECM were examined. Many genes responsible for regulating production and
metabolism of reactive oxygen species (ROS) and ECM remodeling were significantly (p<0.05) altered. To
characterize the metabolic effects of space flight in the skin of mice, global biochemical profiles were
compared in space-flown mice and AEM skin. Of 332 named biochemicals, 19 biochemicals differed
significantly (p<0.05) between space flight skin samples and AEM ground controls. Collectively, the data
demonstrated that space flight condition leads to a shift in homeostasis as the consequence of up/down-
regulation in cellular antioxidants, increases in production of ROS, and tissue remodeling through altered
expression of genes involved in the accumulation and degradation of ECM components. Space flight also
alters several aspects of mouse skin metabolism (redox imbalance). This indicates that astronauts may be
at increased risk for pathophysiologic damage or carcinogenesis in the dermal-tissue.
(PS3-03) Transcriptome profiling and differential gene set enrichment analysis in 3-D epithelial models
following exposure to gamma-ray and HZE particle radiation. Zarana S. Patel, Yared H. Kidane, and Janice
L. Huff, NASA Johnson Space Center / USRA, Houston, TX
Reducing uncertainties in current risk models for assessment of space radiation-induced cancers
requires new knowledge on the fundamental differences in biological responses (the so-called radiation
quality effects) triggered by galactic cosmic rays versus low-LET radiation associated with Earth-based
exposures. In order to characterize radiation quality effects, we are utilizing novel 3-D organotypic human
tissue models for risk assessment as a format for the study of human cells within a realistic tissue
framework; these models help bridge the gap between 2-D monolayer cultures and animal models for risk
extrapolation to humans. To gain insight into potential differences in the biological response of cells to
HZE particle radiation compared to low-LET gamma-rays, we performed global gene expression profiling
of esophageal epithelial cells grown in 3-D cultures at 72 hours following exposure to equitoxic doses of
137Cs gamma-rays or 48Ti ions (350 MeV/u) using Illumina platform (HT12 Expression Beadchip) arrays.
Functional gene set enrichment analysis (GSEA) was used to identify biological pathway signatures that
were unique to heavy ion particle exposure. We identified 45 statistically significant gene sets at 0.05 q-
value cutoff, including 14 gene sets common to gamma and titanium irradiation, 19 gene sets specific to
gamma-rays, and 12 titanium-specific gene sets. Common gene sets aligned with DNA damage and
immune system and inflammatory cytokine pathway activation. The top gene set enriched for the gamma-
irradiated samples involved KRAS pathway activation, with overall enrichment in genes related to
extracellular matrix regulation. For titanium exposure, the top ranking gene set contained genes whose
expression was increased in TNF-treated cells, with overall enrichment in genes involved in TGF-β and
cytokine pathways. These results suggest that GSEA is a powerful approach for assessing the functional
significance of radiation quality-dependent changes from datasets where the changes are subtle but
broad, and where analysis based on rankings of single gene fold-changes may not reveal important
biological information.
189 | P a g e
