HORMONAL AND SUBSTRATE REGULATION OF 3-THIA FATTY-ACID METABOLISM IN MORRIS-7800 C1 HEPATOMA-CELLS

The 3-thia fatty acid tetradecylthioacetic acid (TTA) has recently bee n shown to inhibit growth rate and increase peroxisomal acyl-CoA oxida se (ACO) (EC 1.3.99.3) activity in the Morris 7800 C1 hepatoma cells. Dexamethasone potentiates and insulin antagonizes these effects of TTA . We demonstrate here the metabolism of the 3-thia acids in these cell s and the influence of insulin and dexamethasone on this. (1) The Morr is 7800 C1 hepatoma cells exhibited a low omega-hydroxylation activity of the 3-thia acid (and lauric acid). The combination of TTA and dexa methasone induced the omega-hydroxylation and ACO activities in these cells. TTA alone induced ACO activity, but not omega-hydroxylation act ivity. Insulin counteracted the induction of both enzyme activities. T hese results indicate that these two enzyme activities are under simil ar but independent regulation. (2) Hepatoma cells grown with 80 muM Tr A in the medium accumulated phospholipids containing the 3-thia fatty acid. After 7 days, TTA accounted for approx. 40 % of the total fatty acids in the phospholipids. In addition, TTA affected the incorporatio n of endogenous fatty acids into phospholipids by decreasing the amoun ts of palmitic (C-16:0) and vaccenic (C18:1(n-7)) acid and increasing the amounts of linoleic (C18:2(n-6)) and alpha-linolenic (C18:3(n-3)) acid in the phospholipids. (3) Dexamethasone increased the incorporati on of labelled TTA into both phospholipids and triacylglycerol. Most o f the labelled triacylglycerol formed was secreted into the medium. In sulin increased the incorporation of labelled TTA into triacylglycerol , but not into phospholipids. The labelled triacylglycerol formed was retained in the cells.