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intestinal pathologies, there are very few studies on long-term effects of radiation, fewer involved a
therapeutically relevant γ radiation dose, and none explored persistent tissue metabolomic alterations
after heavy ion space radiation exposure. Using a metabolomics approach, we report long-term
metabolomic markers of radiation injury and perturbation of signaling pathways linked to metabolic
alterations in mice after heavy ion or γ radiation exposure. Intestinal tissues (C57BL/6J, female, 6 to 8 wks)
were analyzed using ultra performance liquid chromatography coupled with electrospray quadrupole
time-of-flight mass spectrometry (UPLC-QToF-MS) two months after 2 Gy γ radiation and results were
compared to an equitoxic 56Fe (1.6 Gy) radiation dose. The biological relevance of the metabolites was
determined using Ingenuity Pathway Analysis, immunoblots, and immunohistochemistry. Metabolic
profile analysis showed radiation-type-dependent spatial separation of the groups. Decreased adenine
and guanosine and increased inosine and uridine suggested perturbed nucleotide metabolism. While both
radiation types affected amino acid metabolism, 56Fe radiation preferentially altered dipeptide
metabolism. Furthermore, 56Fe radiation caused upregulation of ‘prostanoid biosynthesis’ and
‘eicosanoid signaling’, which are interlinked events related to cellular inflammation and have implications
for nutrient absorption and inflammatory bowel disease during space missions and after radiotherapy. In
conclusion, our data showed for the first time that metabolomics can not only be used to distinguish
between heavy ion and γ radiation exposures, but also as a radiation-risk assessment tool for intestinal
pathologies through identification of biomarkers persisting long after exposure.



(PS3-13) The impact of age, radiation quality, and tissue type in the induction of centrosome
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aberrations. Janice M. Pluth ; Deepa M. Sridharan ; Mary K. Whalen ; Lori J. Chappell ; and Francis A.
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Cucinotta LBNL, Berkeley, CA ; NASA, Lyndon B. Johnson Space Center, Houston, TX ; and University of
Nevada, Las Vegas, NV
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Centrosome amplification, or the formation of additional or aberrantly large centrosomes, has
been observed in both pre-malignant and malignant states and correlates with cancer progression.
Centrosome amplification is also induced following exposure to ionizing radiation. In this study we are
investigating whether differences in tissue type and radiation quality significantly affect the levels of
centrosome amplifications in finite lifespan, isogenic, human mammary epithelial and fibroblast cells
following radiation exposure. Additionally, we are examining whether higher levels of DNA damage
signaling is evident in cells exhibiting radiation-induced centrosome aberrations. Lastly, we are studying
how the age of the individual the cells were isolated from impacts the sensitivity of radiation-induced
centrosome aberrations. To address these questions, primary mammary (HMEC) or mammary fibroblast
(HMF) cells were irradiated and cultured for various times post irradiation and then dually stained for
proteins of interest for immunofluorescence analysis. The effect of different doses and radiation qualities
of radiation were also studied using X-ray, as well as various high LET radiation exposures, including iron
ions (1 GeV/u), silicon ions (93 MeV/u), or titanium ions (300 MeV/u). Preliminary work reveals that
radiation quality plays an important role in the level of centrosome amplifications. Additionally, cell type
appears to be key in that fibroblast cells appear more resistant to forming radiation-induced centrosome
aberrations. Furthermore, levels of γH2AX were higher in cells displaying centrosome aberrations,
suggesting that persistent DNA damage signaling may play a role either as a mediator or as a consequence
of the processes involved in centrosome amplification. The association between centrosome
amplifications and the presence of increased levels of persistent DNA damage signaling is significant
because it provides a better understanding of the underlying mechanistic reasons for aberrant





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