Fatty acid composition of microsomal and soluble fractions of mammary adenocareinomas in mice

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Authors
Raines, Gloria Mae Kinnett
Advisor
Bennett, Alice S.
Issue Date
1976
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Degree
Thesis (M.S.)
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Abstract

It has been suggested that membrane characteristics associated with carcinomas could be related to an altered molecular structure of lipids inplasma membrane. The microsomal and soluble fractions of the cell are major sites of de novo synthesis and elongation/desaturation of fatty acids. It was the purpose of this study to compare the fatty acid composition of microsomal and soluble fractions isolated from mammary adenocarcinomas with that of normal mammary tissue and to determine if deviations found in the plasma membrane isolated from tumors could be observed at these subcellular levels.Microsomal and soluble fractions were isolated by differential centrifugation from mammary adenocarcinomas and from normal mammary tissue of Strain A female mice. Activities of nicotinamide adenine dinucleotide, reduced (NADH) dependent cytochrome c reductase andnicotinamide adenine dinucleotide phosphate, reduced (NADPH) dependent cytochrome c reductase in these fractions were determined. The fatty acids were extracted, methylated, and methyl esters identified and quantified using gas liquid chromatography. Polar and non-polar GLC columns, silver nitrate thin layer chromatography, hydrogenation, and spiking was used to confirm the identity of some fatty acids.Fatty acid composition of the microsomal and soluble fractions was similar in tumor and normal tissue. There was a greater percentage of C24:1 in tumors. A reversal of the oleic to stearic acid ratio, an increase in the level of palmitic acid, and a tendency toward long chain polyenoic fatty acids, as reported in studies on the plasma membrane isolated from tumors, was not evident in either the microsomal or soluble fractions. There was evidence of greater utilization of NADPH in the reduction of cytochrome c reductase in tumors. This may result in a decreased availability of NADPH for fatty acid synthetase and lipogenesis.Results of this study do not demonstrate support for a shift in the biosynthetic pathway for the synthesis of fatty acids in carcinomas. It is possible that changes in the lipid composition in the plasma membrane of tumor cells occur after initial incorporation or a shift in biosynthesis could occur in the mitochondria, another site of de novo synthesis and elongation/desaturation of fatty acids.

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