Document Detail


In vivo MRS assessment of altered fatty acyl unsaturation in liver tumor formation of a TGF alpha/c-myc transgenic mouse model.
MedLine Citation:
PMID:  19065002     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Current detection methods (computed tomography, ultrasound, and MRI) for hepatocarcinogenesis in humans rely on visual confirmation of neoplastic formations. A more effective early detection method is needed. Using in vivo magnetic resonance spectroscopy (MRS), we show that alterations in the integral ratios of the bis-allyl to vinyl hydrogen protons in unsaturated lipid fatty acyl groups correlate with the development of neoplastic formations in vivo in a TGFalpha/c-myc mouse hepatocellular carcinoma (HCC) model. HPLC analysis of the TGFalpha/c-myc mice liver tissue revealed a significant increase in the amount of oleic acid, along with alterations in linoleic and gamma-linolenic acids, as compared with control CD1 mice. Electrospray ionization tandem mass spectrometry analysis indicated a significant increase in the abundance of specific glycerol phosphatidylcholine (GPCho) lipids containing palmitic and oleic acids between control CD1 and TGFalpha/c-myc mice liver tissue extracts. Western blot analysis of the mice liver tissue indicates alterations in the desaturase enzyme stearoyl CoA desaturase (SCD)1, responsible for palmitic and oleic acid formation. Microarray analysis detected alterations in several genes involved with fatty acid metabolism, particularly SCD2, in transgenic mouse liver tissue. In correlation with the HPLC, mass spectrometry, Western blot, and microarray analyses, we are able to confirm the ability of in vivo MRS to detect precancerous lesions in the mouse liver before visual neoplastic formations were detectable by MRI.
Authors:
J Griffitts; Y Tesiram; G E Reid; D Saunders; R A Floyd; R A Towner
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2008-12-08
Journal Detail:
Title:  Journal of lipid research     Volume:  50     ISSN:  0022-2275     ISO Abbreviation:  J. Lipid Res.     Publication Date:  2009 Apr 
Date Detail:
Created Date:  2009-03-19     Completed Date:  2009-06-22     Revised Date:  2010-09-23    
Medline Journal Info:
Nlm Unique ID:  0376606     Medline TA:  J Lipid Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  611-22     Citation Subset:  IM    
Affiliation:
Advanced Magnetic Resonance Center, Oklahoma Medical Research Foundation, Oklahoma City, OK 73104, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Blotting, Western
Chromatography, High Pressure Liquid
Fatty Acids, Unsaturated / chemistry,  metabolism*
Genes, myc*
Liver Neoplasms, Experimental / genetics*,  metabolism*,  pathology
Magnetic Resonance Imaging
Magnetic Resonance Spectroscopy
Male
Mice
Mice, Transgenic
Oligonucleotide Array Sequence Analysis
Spectrometry, Mass, Electrospray Ionization
Tandem Mass Spectrometry
Transforming Growth Factor alpha / genetics*
Grant Support
ID/Acronym/Agency:
R01CA82506/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/Fatty Acids, Unsaturated; 0/Transforming Growth Factor alpha
Comments/Corrections

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