TOXICITY OF POLYUNSATURATED FATTY-ACID ESTERS FOR HUMAN MONOCYTE-MACROPHAGES - THE ANOMALOUS BEHAVIOR OF CHOLESTERYL LINOLENATE

We have investigated the toxicity to human manocyte-macrophages, and s usceptibility to oxidation, of different individual dietary fatty acid s in cholesterol esters and triglycerides, added to the cell cultures as coacervates with bovine serum albumin. Toxicity was assessed using release of radioactivity from cells preloaded with tritiated adenine. Lipid oxidation was measured by gas chromatography (GC). The triglycer ides showed a direct relationship between toxicity and increasing unsa turation, which in turn correlated with increasing susceptibility to o xidation. Triolein (18:1; omega-9) and trilinolein (18:2; omega-6) wer e non-toxic. Trilinolenin (18:3; omega-3) was toxic only after prolong ed incubation. Triarachidonin (20:4; omega-6), tridocosapentaenoin (20 :5; omega-3) and tridocosahexaenoin (22:6; omega-3) were profoundly an d rapidly toxic. There was a similar relationship between toxicity and increasing unsaturation for most of the cholesterol esters, but chole steryl linolenate was apparently anomalous, being non-toxic in spite o f possessing three double bonds and being extensively oxidised. Probuc ol and DL-a-tocopherol conferred protection against the toxicity of ch olesteryl arachidonate and triarachidonin. The oxidation in these expe riments was largely independent of the presence of cells. GC indicated that formation of 7-oxysterols might contribute to the toxicity of ch olesteryl linoleate. The toxicity of triglycerides suggests that polyu nsaturated fatty acid peroxidation products are also toxic. Possible m echanisms of cytotoxicity and relevance to atherosclerosis are discuss ed.