Abstract

Due to the potential risk of accidental exposure to gamma radiation, it’s critical to identify the biomarkers of radiation exposed creatures. In the present study, NMR based metabolomics combined with multivariate data analysis to evaluate the metabolites changed in the C57BL/6 mouse spleen after 4 days whole body exposure to 3.0 Gy and 7.8 Gy gamma radiations. Principal component analysis (PCA) and orthogonal projection to latent structures analysis (OPLS) are employed for classification and identification potential biomarkers associated with gamma irradiation. Two different strategies for NMR spectral data reduction (i.e., spectral binning and spectral deconvolution) are combined with normalize to constant sum and unit weight before multivariate data analysis, respectively. The combination of spectral deconvolution and normalization to unit weight is the best way for identifying discriminatory metabolites between the irradiation and control groups. Normalized to the constant sum may achieve some pseudo biomarkers. PCA and OPLS results shown that the exposed groups can be well separated from the control group. Leucine, 2-aminobutyrate, valine, lactate, arginine, glutathione, 2-oxoglutarate, creatine, tyrosine, phenylalanine, π-methylhistidine, taurine, myoinositol, glycerol and uracil are significantly elevated while ADP is decreased significantly. These significantly changed metabolites are associated with multiple metabolic pathways and may be potential biomarkers in the spleen exposed to gamma irradiation.

Highlights

  • In our daily life, the potential risk of accidental exposure to ionized radiation is increasing [1]

  • The peak intensities are normalized to unit weight of spleen tissue before extraction, so the peak intensities in the spectra of radiation group and those of the control group can be directly compared visually

  • We have shown that the combined application of 1H NMR metabolomics and multivariate data analysis (e.g. Principal component analysis (PCA) and orthogonal projection to latent structures analysis (OPLS)) is a powerful tool for exploring gamma irradiation induced metabolites changed in mouse spleen (Figure 4)

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Summary

Introduction

The potential risk of accidental exposure to ionized radiation is increasing [1]. Gamma radiation is a major component of ionized radiation from the nuclear accident. Understand the biological impact of gamma radiation to mammal is importance for developing medical counter measures to mitigate the damage from gamma radiation. To achieve this goal, it’s critical to understand thoroughly the biological respond at molecular level, including identify potential biomarkers of radiation exposed creatures for accurate assessment. Gamma radiation disturbances have serious consequences on the whole immune system [3] and the spleen plays important roles in immune system

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