Effect of essential fatty acid deficiency on the lipid composition of the Yoshida ascites hepatoma (AH 130) and of the liver and blood plasma from host and normal rats1

In order to study the response of a poorly differentiated tumor to nutritional manipulation, the Yoshida ascites hepatoma (AH 130) was grown in rats fed an essential fatty acid (EFA)-deficient diet and in rats fed a control diet. Hepatomas, livers, and blood plasma from host rats and normal rats were studied as to the effects of EFA deficiency on the lipid composition. Normal rats fed an EFA-deficient diet showed an increased concentration of triglycerides and cholesteryl esters in the liver and a reduced level of total phospholipids in plasma. Host rats fed the EFA-deficient diet showed a lower concentration of triglycerides in the liver when compared with the host rats fed a control diet. In addition, EFAdeficient host rats had reduced levels of plasma free fatty acids and triglycerides. These latter were markedly high in host rats under normal dietetic conditions. As compared to the livers of either host rats or normal rats fed the control diet, the Yoshida hepatoma cells had a lower content of total phospholipids and free fatty acids as well as a higher level of free cholesterol; they also showed a typical fatty acid pattern in their phospholipids. The main characteristics of this pattern were a high content of oleic and palmitoleic acids and a low level of Czo and CZ2 polyunsaturated fatty acids. Exposure of Yoshida hepatoma cells to an EFA-deficient environment resulted in a decrease in the concentration of total phospholipids and free fatty acids and in changes in the fatty acid composition similar to those observed in the livers of normal and host rats. These changes suggest that, under the experimental conditions used, the Yoshida hepatoma cells are responsive to EFA deficiency. Supplementary key words ascitic plasma * argentation thinlayer chromatography * liver triglyceride * plasma triglyceride * tumor-bearing animals * oleic acid * eicosatrienoic acid * triene: tetraene ratio interesting examples of this defective metabolic regulation in the lipid metabolism of several hepatomas such as the loss of the normal inhibition of cholesterol biosynthesis by dietary cholesterol (2-4) and the lack of adaptation to nutritional manipulations that affect the fatty acid biosynthesis (4-8). T h e responsiveness of tumor cells to nutritional manipulations was also assessed by studying the changes in their lipid composition after exposure to essential fatty acid (EFA) deficiency, which induces a typical lipid pattern in normal tissues (917) through the induction of adaptative mechanisms (18-22). However studies on the growth of several tumors in EFA-deficient host animals (7, 8, 23-25) have given conflicting results as to the fatty acid composition. This may have been due to differences either in the experimental conditions (time-course of dietetic treatment, etc.) or in the characteristics of the tumor studied (degree of differentiation, solid or ascitic