Incorporation and metabolism of exogenous fatty acids by cultured normal and tumoral glial cells.

We have investigated the transformation of exogenous radioactive free fatty acids by cultured glial cells and their incorporation into complex lipids. The cells were either tumor lines (C6 and NN) or primary cultures from newborn rat hemispheres. The tumor lines could undergo morphological differentiation with dibutyryl cyclic AMP or bromodeoxyuridine. The fatty acid precursors used were palmitic, stearic, oleic, linoleic and linolenic acids. Tumor cells presented a higher incorporation of the precursors in the cell lipid acyl groups than did normal cells. Tumor cells desaturated and/or elongated palmitic, stearic and oleic acid to a higher extent than did normal cells. In contrast, tumor cells transformed linoleic and linolenic acids to their polyunsaturated derivatives to a lower extent than did normal cells. In differentiated tumor cells, these patterns of metabolism were shifted toward the patterns of normal cells. Tumor cells did not exhibit delta 4-desaturase activity, but such activity was restored in the C6 line upon dibutyryl cyclic AMP-induced differentiation. Transformation of linoleic and linolenic acid is likely to proceed through initial delta 6 desaturation. Phospholipids were preferentially labelled with the radioactive fatty acids, and only a little radioactivity was found in the neutral lipid fraction, mainly in diacylglycerols. Each fatty acid precursor label was incorporated in individual phospholipids to a proportion which reflected the typical acyl group composition of glycerophospholipids; we observed high levels of incorporation of palmitic acid and its derivatives into choline glycerophospholipids, and high levels of incorporation of linolenic acid and its derivatives into ethanolamine glycerophospholipids. This pattern was more marked in tumor cells than in normal cells, and the differentiation of tumor cells partially restored the normal pattern, mainly in bromodeoxyuridine-treated NN cells. Both types of differentiation of glial cell lines can be useful as models for the understanding of membrane physiology in normal and tumor cells.