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.