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Lipid Metabolism in Cultured Cells: Growth of Tumor Cells Deficient in Essential Fatty Acids¹

Department of Biochemistry, The George Washington University School of Medicine, Washington, D. C. 20005

Certain strains of cells have been grown in tissue culture in lipid-free synthetic media, whereas others appear to require essential fatty acids. Growth of two rapidly dividing ascites tumors, Ehrlich ascites carcinoma and Sarcoma 180, was therefore studied in normal mice and in mice with pronounced essential fatty acid deficiency. Essential fatty acids in blood lipids of essential fatty acid-deficient mice comprised only 2% of the total, as compared to more than 30% of the total in normal mice. The mean generation time of Ehrlich ascites carcinoma cells grown in essential fatty acid-deficient mice (1.07 ± 0.19 days) was not significantly different from that of normal cells grown in normal mice (1.04 ± 0.19 days). Comparable results were also obtained with the ascitic form of Sarcoma 180. Transplantability was unaffected by essential fatty acid deficiency, as evidenced by normal growth when deficient cells were used as inoculum.

Fatty acid composition of tumor cell lipids was determined by gas-liquid chromatography. The total lipid content of the tumors was unchanged, whereas the average content of essential fatty acids, linoleic and arachidonic, was decreased from approximately 36% of the total in normal mice to less than 3% in tumor cells grown in deficient host mice. These changes were accompanied by major increases in the content of oleic acid (18:1) (from 24 to 42%) and eicosatrienoic acid (20:3) (from 0 to 14%). When deficient cells were transplanted into normal mice, the fatty acid composition returned to normal within 72 hr. Unaltered growth of cells in association with these changes in fatty acid composition suggests that oleic and eicosatrienoic acids may fulfill certain of the structural or metabolic functions of the "essential" fatty acids in these two strains of tumor cells.

¹ This work was supported by USPHS Grants HE-05062, AM-10082, and 5K3-16730. This is Paper 8 of a series. The preceding paper of the series is Reference 1.

Received 7/24/70. Accepted 9/23/70.