Carcinogenesis, Vol. 22, No. 5, 795-804,
May 2001
© 2001 Oxford University Press
CARCINOGENESIS |
Changes in essential fatty acid patterns associated with normal liver regeneration and the progression of hepatocyte nodules in rat hepatocarcinogenesis
Programme on Mycotoxins and Experimental Carcinogenesis,
1 National Research Programme for Nutritional Intervention,
2 Experimental Biology Programme–Primate Unit, Medical Research Council (MRC) ,PO Box 19070, Tygerberg 7505, South Africa
Changes in lipid metabolism were monitored in rat hepatocyte nodules at certain time points over 9 months. Tissue obtained from partially hepatectomized rats, collected over a period of 7 days, were included as a control for normal hepatocyte cell proliferation. Two important features regarding the lipid profiles of hepatocyte nodules and normal regenerating liver were the increased concentrations of phosphatidylethanolamine (PE), resulting in a decreased phosphatidylcholine/phosphatidylethanolamine (PC/PE) ratio, and cholesterol. These changes coincided with increased membrane fluidity in the nodules and regenerating liver. With respect to the fatty acid (FA) profiles of the nodules, C18:1
9 and C18:26 increased in PE and PC whereas C20:46 decreased in PC and increased in PE. C22:56 and C22:63, the end products of the 6 and 3 metabolic pathways, respectively, decreased in PC and remained unchanged in PE. The FA levels in PC reflected an impaired 
-6 desaturase enzyme, whereas this effect was masked in PE due to the increased concentration of this phospholipid fraction. In regenerating liver, the FA profiles of PC and PE showed the same pattern as described for the hepatocyte nodules, except for C18:19 which decreased in PC and increased non-significantly in PE. The increased C18:19 level, a FA with anti-oxidative properties, as well as the decreased levels of the long-chain polyunsaturated fatty acids (C20 and C22 carbon chains), have been associated with the decreased lipid peroxidation level in hepatocyte nodules. The resultant decrease in peroxidative metabolites, known to affect apoptosis, could be important in the progression of the nodules into neoplasia. The present results indicate that the altered lipid parameters associated with hepatocyte nodules closely mimics cellular proliferation in regenerating liver and could be responsible for the enhanced proliferation and/or altered growth pattern in these lesions. The altered FA profiles suggest various pathways in which FA could play a role in transmembrane signalling related to the altered cell proliferative and apoptotic pathways. The persistent changes in the hepatocyte nodules suggest that the lipid metabolism escapes the regulatory mechanisms required for normal cellular homeostasis at different levels.
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