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Title: 137 Cs γ Ray and 28 Si Irradiation Induced Murine Hepatocellular Carcinoma Lipid Changes in Liver Assessed by MALDI-MSI Combined with Spatial Shrunken Centroid Clustering Algorithm: A Pilot Study

Abstract

Characterization of lipids by matrix-assisted laser desorption ionization mass spectrometry imaging (MALDI-MSI) is of great interest because not only are lipids important structural molecules in both the cell and internal organelle membranes, but they are also important signaling molecules. MALDI-MSI combined with spatial image segmentation has been previously used to identify tumor heterogeneities within tissues with distinct anatomical regions such as the brain. However, there has been no systematic study utilizing MALDI-MSI combined with spatial image segmentation to assess the tumor microenvironment in the liver. Here, we present that image segmentation can be used to evaluate the tumor microenvironment in the liver. In particular, to better understand the molecular mechanisms of irradiation-induced hepatic carcinogenesis, we used MALDI-MSI in the negative ion mode to identify lipid changes 12 months post exposure to low dose 28Si and 137Cs γ ray irradiation. We report here the changes in the lipid profiles of male C3H/HeNCrl mice liver tissues after exposure to irradiation and analyzed using the spatial shrunken centroid clustering algorithm. These findings provide valuable information as astronauts will be exposed to high-charge high-energy (HZE) particles and low-energy γ-ray irradiation during deep space travel. Even at low doses, exposure to these irradiations can leadmore » to cancer. Previous studies infer that irradiation of mice with low-dose HZE particles induces oxidative damage and microenvironmental changes that are thought to play roles in the pathophysiology of hepatocellular carcinoma.« less

Authors:
ORCiD logo [1];  [2];  [3]; ORCiD logo [4]
+ Show Author Affiliations
  1. Biochemistry and Molecular Biology, The University of Texas Medical Branch, Galveston, Texas 77555, United States
  2. Pharmacology and Toxicology, The University of Texas Medical Branch, Galveston, Texas 77555, United States
  3. The Radiation Effects Research Foundation (RERF), Hiroshima and Nagasaki 732-0815, Japan
  4. Biochemistry and Molecular Biology, The University of Texas Medical Branch, Galveston, Texas 77555, United States, Pharmacology and Toxicology, The University of Texas Medical Branch, Galveston, Texas 77555, United States, Radiation Oncology, The University of Texas Medical Branch, Galveston, Texas 77555, United States
Publication Date:
Research Org.:
Florida State Univ., Tallahassee, FL (United States)
Sponsoring Org.:
USDOE Office of Science (SC), Basic Energy Sciences (BES)
OSTI Identifier:
1664539
Alternate Identifier(s):
OSTI ID: 1670687
Grant/Contract Number:  
HS0000031
Resource Type:
Published Article
Journal Name:
ACS Omega
Additional Journal Information:
Journal Name: ACS Omega Journal Volume: 5 Journal Issue: 39; Journal ID: ISSN 2470-1343
Publisher:
American Chemical Society (ACS)
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; Anatomy; Lipids; Ions; Tumors; Irradiation

Citation Formats

Nia, Anna M., Shavkunov, Alexander, Ullrich, Robert L., and Emmett, Mark R. 137 Cs γ Ray and 28 Si Irradiation Induced Murine Hepatocellular Carcinoma Lipid Changes in Liver Assessed by MALDI-MSI Combined with Spatial Shrunken Centroid Clustering Algorithm: A Pilot Study. United States: N. p., 2020. Web. doi:10.1021/acsomega.0c03047.
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Nia, Anna M., Shavkunov, Alexander, Ullrich, Robert L., & Emmett, Mark R. 137 Cs γ Ray and 28 Si Irradiation Induced Murine Hepatocellular Carcinoma Lipid Changes in Liver Assessed by MALDI-MSI Combined with Spatial Shrunken Centroid Clustering Algorithm: A Pilot Study. United States. https://doi.org/10.1021/acsomega.0c03047
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Nia, Anna M., Shavkunov, Alexander, Ullrich, Robert L., and Emmett, Mark R. Tue . "137 Cs γ Ray and 28 Si Irradiation Induced Murine Hepatocellular Carcinoma Lipid Changes in Liver Assessed by MALDI-MSI Combined with Spatial Shrunken Centroid Clustering Algorithm: A Pilot Study". United States. https://doi.org/10.1021/acsomega.0c03047.
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@article{osti_1664539,
title = {137 Cs γ Ray and 28 Si Irradiation Induced Murine Hepatocellular Carcinoma Lipid Changes in Liver Assessed by MALDI-MSI Combined with Spatial Shrunken Centroid Clustering Algorithm: A Pilot Study},
author = {Nia, Anna M. and Shavkunov, Alexander and Ullrich, Robert L. and Emmett, Mark R.},
abstractNote = {Characterization of lipids by matrix-assisted laser desorption ionization mass spectrometry imaging (MALDI-MSI) is of great interest because not only are lipids important structural molecules in both the cell and internal organelle membranes, but they are also important signaling molecules. MALDI-MSI combined with spatial image segmentation has been previously used to identify tumor heterogeneities within tissues with distinct anatomical regions such as the brain. However, there has been no systematic study utilizing MALDI-MSI combined with spatial image segmentation to assess the tumor microenvironment in the liver. Here, we present that image segmentation can be used to evaluate the tumor microenvironment in the liver. In particular, to better understand the molecular mechanisms of irradiation-induced hepatic carcinogenesis, we used MALDI-MSI in the negative ion mode to identify lipid changes 12 months post exposure to low dose 28Si and 137Cs γ ray irradiation. We report here the changes in the lipid profiles of male C3H/HeNCrl mice liver tissues after exposure to irradiation and analyzed using the spatial shrunken centroid clustering algorithm. These findings provide valuable information as astronauts will be exposed to high-charge high-energy (HZE) particles and low-energy γ-ray irradiation during deep space travel. Even at low doses, exposure to these irradiations can lead to cancer. Previous studies infer that irradiation of mice with low-dose HZE particles induces oxidative damage and microenvironmental changes that are thought to play roles in the pathophysiology of hepatocellular carcinoma.},
doi = {10.1021/acsomega.0c03047},
journal = {ACS Omega},
number = 39,
volume = 5,
place = {United States},
year = {Tue Sep 22 00:00:00 EDT 2020},
month = {Tue Sep 22 00:00:00 EDT 2020}
}
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Journal Article:
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Publisher's Version of Record
https://doi.org/10.1021/acsomega.0c03047
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Figures / Tables:

Figure 1 Figure 1: Segmentation result of the MALDI-MSI dataset using the SSCCA. (a) There are two biological replicates from the tumor sections of 28Siirradiated, two biological replicates from the tumor sections of 137Cs γ ray-irradiated, and three biological replicates from healthy nonirradiated control murine liver tissues. The segmentation with spatial shrunkenmore » centroids and structurally adaptive distance selected five tissue segments that are color-coded. The colors correspond to numbers in the bottom figure legend (b), which represent segments 1 (orange), 2 (green), 3 (light blue), 4 (pink), and 5 (dark blue). Segment 1 (orange) shows the core tumor/HCC region on each tumor specimen, where the disease-looking part of the specimen was observed both histologically (H&E staining) and visible by the naked eye on the MALDI slide. Segment 2 (green), segment 3 (light blue), and segment 4 (pink) show a healthy looking part of the tumor sections as well as in control sections. Segment 5 (dark blue) shows a transition looking part of the specimens in which the tissue looks neither completely healthy nor tumor looking. (b) t-statistics quantified the relative importance of the peaks in each segment. The spectra show that segment 1 (orange/core tumor) is enriched (upregulated) mainly in higher m/z values (∼1400) and downregulated in lower m/z values (<600). Conversely, healthy parts of the tumor sections from irradiated and healthy nonirradiated specimens show upregulation of lower m/z values (<600). (c) H&E slide corresponding to the slide shown in panel (a).« less
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