Effects of Genetic Variation on Urinary Small Molecule Signatures of Mice after Exposure to Ionizing Radiation: A Study of p53 Deficiency.

Metabolites
Evan L PannkukAlbert J Fornace

Abstract

Due to risks from potential exposures to ionizing radiation (IR), improved radiological countermeasures are required, as well as rapid high-throughput biodosimetry. Genotypic variation in the general population contributes to differences in radiosensitivity that may affect biodosimetry accuracy. Previous studies utilized radiosensitive mutant mouse models (Parp1-/- and Atm-/-) to determine the effects of genotypic deficiency on radiation signatures. Here, we extend this approach by examining changes in the urinary metabolome in a hematopoietic (HP) resistant mouse model (p53-/-) after IR exposure. As p53 is a primary regulator in radiation response and apoptosis, limited hematopoietic stem cell apoptosis leads to reduced mortality at doses of ~8-10 Gy but increased mortality at higher doses (> 15 Gy) due to mitotic catastrophe in gastrointestinal (GI) crypt cells. Urine was collected from mice (wild-type (WT), p53+/-, and p53-/-) pre-irradiation and at 4 and 24 h after total body irradiation (TBI) (WT: 8 and 10 Gy; p53-/-: 10 Gy) for metabolic phenotyping using an ultra-performance liquid chromatography mass spectrometry (UPLC-MS) platform. Minimal differences were detected between unirradiated WT, p53+/-, and p53-/- mice. Whil...Continue Reading

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Citations

Aug 17, 2020·Metabolites·Merriline M SatyamitraAndrea L DiCarlo

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Methods Mentioned

BETA
nuclear magnetic resonance
X-ray

Software Mentioned

GraphPad Prism
Random Forests
R
MetaboLyzer
MetaboAnalyst
Random
MassLynx

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