EFFECTS OF PERFLUOROOCTANOIC ACID - A POTENT PEROXISOME PROLIFERATOR IN RAT - ON MORRIS HEPATOMA-7800C1 CELLS, A RAT-CELL LINE

In this study, Morris hepatoma 7800C1 cells (from rat) were exposed to 500 mu M perfluorooctanoic acid (PFOA) in the culture medium for 7 da ys. This treatment resulted in inductions of catalase, lauroyl-CoA oxi dase (which catalyzes the first step in peroxisomal beta-oxidation) an d of cytochrome P-450IVA (specialized for omega-and omega-1 hydroxylat ion of fatty acids). Northern blot analysis revealed that the level of mRNA for peroxisomal fatty acyl-CoA oxidase was enhanced in cells tre ated with PFOA. Inductions of the enzymes mentioned above are generall y connected with peroxisome proliferation in vivo. This work also incl udes a comparison between the activities of catalase, lauroyl-CoA oxid ase, DT-diaphorase and glutathione transferase in rat liver homogenate and 7800C1 cells in order to investigate to what extent this cell lin e differs from the situation in vivo. The findings suggest that the ce lls selectively lost most of their peroxisomes during transformation i nto a cell line and subsequent propagation. The control activities of catalase and lauroyl-CoA oxidase (marker enzymes for peroxisomes) were only about 2% of the corresponding enzyme activities in rat liver. In addition, a morphological study revealed that the frequency of peroxi somes in 7800C1 cells is very low. The control activity of glutathione transferase in 7800C1 cells was 11% of the corresponding activity in rat liver homogenate, whereas the level of DT-diaphorase was virtually the same in 7800C1 cells as in rat liver. Electron microscopic invest igation of the control cultures revealed all signs of viable cells, wi th well-developed cell organelles. Treatment of 7800C1 cells with 500 mu M PFOA has little effect on cellular morphology.