Gangliosides of liver tumors induced by N-2-fluorenylacetamide. II. Alterations in biosynthetic enzymes.
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Biomedical subjects
Publications and source records attributed to W D Merritt.
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Plasma membrane fractions from rat liver exhibited glycosyltransferase activity with endogenous membrane-associated acceptors and either UDP-galactose, UDPglucose, UDP-N-acetylglucosamine, or GDPmannose donors. Of these, incorporation into non-lipid acceptors was most active with UDP-galactose and only with UDPgalactose and UDPmannose was there incorporation into endogenous lipid acceptors. CMP-N-acetylneuraminic acid was inactive as a donor with the isolated plasma membranes. In order to demonstrate transferase activity, low concentrations of substrate sugar nucleotides and short incubation times were used as well as sulfhydryl protectants and a phosphatase inhibitor (NaF) in the reaction mixtures. The findings support the concept of surface localization of at least a galactosyl transferase in cells of rat liver.
Hyperplastic liver nodules induced in rats fed the carcinogen N-2-fluorenylacetamide had levels of total, protein-bound, and ganglioside sialic acid above those of controls. Yet, the total lipid content of hyperplastic nodules and surrounding tissue was nearly identical to the lipid content of control liver. Hyperplastic nodules and surrounding liver did not differ from control tissue in phospholipid distribution patterns or in fatty acid composition of total lipids, neutral lipids, and/or polar lipids. Elevated levels of both free and esterified sterols, and a slightly lower level of phospholipid, were found in both hyperplastic nodules and in surrounding tissue as compared to control liver. The increased sterol ester content was largely due to increased amounts of cholesterol oleate. Thin-layer chromatography of ganglioside extracts revealed all gangliosides of control liver. Amounts of tri- and tetrasialoganglioside were reduced and levels of disialoganglioside were increased in modules relative to both control liver and surrounding tissue. The ganglioside alterations may represent at least one significant minimal deviation of hyperplastic nodules toward the malignant phenotype in keeping with the hypothesis that hyperplastic nodules represent a pre malignant form of hyperplasia.
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