SYNERGISTIC INDUCTION OF ACYL-COA OXIDASE ACTIVITY, AN INDICATOR OF PEROXISOME PROLIFERATION, BY ARACHIDONIC-ACID AND RETINOIC ACID IN MORRIS-HEPATOMA-7800C1 CELLS

Morris hepatoma 7800C1 cells (a Wistar rat cell line) were exposed to 100 mu M arachidonic acid in the medium for seven days. This treatment resulted in 150% and 60% increases (above control activities) in acyl -CoA oxidase (which catalyzes the first step in peroxisomal beta-oxida tion) and catalase activities, respectively. Arachidonic acid (C20:4) can be metabolized to 20- and 19-hydroxy arachidonic acid by cytochrom e P-450IVA and it was shown that our cells are capable of forming 20-h ydroxyarachidonic acid. However, 20-hydroxyarachidonic acid (0.1-0.8 m u M, 4 days) had no effects on lauroyl-CoA oxidase and catalase activi ties in Morris hepatoma cells. Treatment of 7800C1 cells with 100 mu M all-trans-retinoic acid resulted in inductions of catalase (160% abov e the control activity) and carnitine acetyltransferase (140% above th e control activity) activities. The activity of lauroyl-CoA oxidase wa s often, but not always, slightly induced by treatment with all-trans- retinoic acid. When all-trans-retinoic acid was administered together with arachidonic acid, these two compounds had a synergistic effect on the induction of acyl-CoA oxidase activity (almost 700% above the con trol activity). However, treatment of Morris hepatoma cells with the m an-made peroxisome proliferator, perfluorooctanoic acid, together with all-irans-retinoic acid did not result in any synergistic effect on t his same enzyme activity. In summary, this study (1) corroborates find ings from transfection experiments indicating that the heterodimer PPA R-RXR alpha activates transcription of the acyl-CoA oxidase gene using the Morris hepatoma cell line; (2) shows that arachidonic acid induce s the activity of lauroyl-CoA oxidase; (3) suggests that transcription of the catalase gene is not regulated by a PPAR-RXR alpha heterodimer in this system; and (4) demonstrates that peroxisome proliferation in Morris hepatoma cells by perfluorooctanoic acid is nor as dependent o n the level of retinoic acid as is the same process caused by arachido nic acid.