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Lipid Compositions of Intracellular Membranes Isolated from Rat Liver Nodules in Wistar Rats¹

Department of Diagnostic Radiology at Karolinska Hospital, Karolinska Institutet, Stockholm [J. M. O.]; Department of Pathology, Clinical Research Center at Huddinge Hospital, Karolinska Institutet, Huddinge [L. C. E.]; and Department of Biochemistry, University of Stockholm, S-106 91, Stockholm [J. M. O., G. D.], Sweden

The mevalonate pathway gives rise to important end products for the regulation of growth and resistance to oxidative stress and is, consequently, of importance in carcinogenesis. In this study liver nodules were produced in Wistar rats by intermittent feeding with dietary 2-acetylaminofluorene, and the lipid compositions of isolated microsomes, mitochondria, and lysosomes were examined. The phospholipid compositions of these subfractions were unchanged compared to normal hepatic tissue, but the fatty acid patterns were altered, particularly in microsomes. An increase in the content of palmitic acid and a decrease in that of stearic acid were noted. The pattern of fatty acyl moleties on carbon atoms 1 and 2 of the glycerol backbone of phospholipids was unchanged in nodular tissue compared to normal liver. The amount of dolichol was significantly higher in microsomes and mitochondria, but not in lysosomes, and the relative amounts of longer polyisoprenoid compounds were increased in the liver nodules. The relative concentration of esterified dolichol was decreased and an enrichment in saturated fatty acids in this fraction could be observed. The cholesterol concentration was found to be lower in microsomes, but was unchanged in mitochondria and lysosomes, and the normally low concentration of cholesteryl esters was elevated somewhat in microsomes and lysosomes. The ubiquinone content of liver nodular mitochondria was unchanged, but increased 7-fold in microsomes and 2-fold in lysosomes. The alterations found in the lipid composition of liver nodules are significant and have functional implications in many cellular processes of proposed importance for the carcinogenic process, i.e., protein glycosylation cholesterogenesis, regulation of the mevalonate pathway, cellular oxidation-reduction state, and resistance to oxidative stress.

¹ Supported by grants from the Swedish Cancer Society (to G. D.) and the Swedish Medical Research Council (to L. C. E.).

² To whom requests for reprints should be addressed.

Received 1/ 3/91. Accepted 5/ 3/91.

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