Long-Term Differential Changes in Mouse Intestinal Metabolomics after γ and Heavy Ion Radiation Exposure

• DOI: 10.1371/journal.pone.0087079
• Publication Date: 2014-01-27T21:43:51Z
• Authors: Amrita K. Cheema; Shubhankar Suman; Prabhjit Kaur; Rajbir Singh; Albert J. Fornace; Kamal Datta
• Keywords: 0301 basic medicine; Science; Q; Immunoblotting; R; Immunohistochemistry; Mass Spectrometry; 3. Good health; Mice, Inbred C57BL; Mice; Radiation Injuries, Experimental; 03 medical and health sciences; Gene Expression Regulation; Gamma Rays; Medicine; Animals; Metabolomics; Female; Heavy Ions; Amino Acids; Intestinal Mucosa; Chromatography, High Pressure Liquid; Research Article

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