Fatty acid specificity in the inhibition of cell proliferation and its relationship to lipid peroxidation and prostaglandin biosynthesis.

Primary cultures of smooth muscle cells were established from the medial layer of guinea pig aorta. Cells at passage level 4 were treated with different series of fatty acids belonging to the n-9, n-6 and n-3 families. Lipid peroxidation was measured by the thiobarbituric acid assay and prostaglandin biosynthesis was measured by the radioimmunoassay of PGE and 6-keto-PGF1 alpha. Cell proliferation was estimated from the total cell number of cultures seeded at low density. 18:1(n-9) did not form lipid peroxides and this fatty acid stimulated cell proliferation. All fatty acids which generated lipid peroxides inhibited cell proliferation, but inhibition was correlated with the degree of lipid peroxidation only in the n-9 fatty acid family. 22:4(n-6) and 22:6(n-3) inhibited prostaglandin biosynthesis. 18:2(n-6), 18:2(n-9), 18:3(n-3), 20:2(n-9), 20:3(n-3) and 20:5(n-3) had no effect on prostaglandin biosynthesis. 18:3(n-6), 20:3(n-6) and 20:4(n-6) generated prostaglandins. 20:3(n-9) generated metabolites with prostaglandin immunoreactivity. The inhibition of cell proliferation did not correlate with enhanced or inhibited prostaglandin synthesis. The inhibition of cell proliferation was related to the structures of the different polyunsaturated fatty acid families decreasing in the order n-9 greater than n-6 greater than n-3. Eicosatrienoic acids were the most effective inhibitors of cell proliferation in each fatty acid family and 20:3(n-9) was the most potent eicosatrienoic acid. These data show that specific as yet unrecognized products of fatty acid metabolism are responsible for the inhibition of cell proliferation.