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 microM perfluorooctanoic acid (PFOA) in the culture medium for 7 days. This treatment resulted in inductions of catalase, lauroyl-CoA oxidase (which catalyzes the first step in peroxisomal beta-oxidation) and of cytochrome P-450IVA (specialized for omega- and omega-1 hydroxylation of fatty acids). Northern blot analysis revealed that the level of mRNA for peroxisomal fatty acyl-CoA oxidase was enhanced in cells treated with PFOA. Inductions of the enzymes mentioned above are generally connected with peroxisome proliferation in vivo. This work also includes a comparison between the activities of catalase, lauroyl-CoA oxidase, DT-diaphorase and glutathione transferase in rat liver homogenate and 7800C1 cells in order to investigate to what extent this cell line differs from the situation in vivo. The findings suggest that the cells selectively lost most of their peroxisomes during transformation into 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 peroxisomes 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 investigation of the control cultures revealed all signs of viable cells, with well-developed cell organelles. Treatment of 7800C1 cells with 500 microM PFOA has little effect on cellular morphology.
Department of Biochemistry, Wallenberg Laboratory, Stockholm University, Sweden.
A K
AK
Sohlenius
K
K
Andersson
A
A
Bergstrand
O
O
Spydevold
J W
JW
De Pierre
D042962:Acyl-CoA Oxidase; D000818:Animals; D002210:Caprylates / Q000494:pharmacology*; D003577:Cytochrome P-450 Enzyme System / Q000032:analysis; D005466:Fluorocarbons / Q000494:pharmacology*; D005982:Glutathione Transferase / Q000032:analysis; D008297:Male; D008830:Microbodies / Q000187:drug effects* / Q000201:enzymology; D010088:Oxidoreductases / Q000032:analysis* / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D018160:Receptors, Cytoplasmic and Nuclear / Q000187:drug effects; D014157:Transcription Factors / Q000187:drug effects; D014407:Tumor Cells, Cultured / Q000648:ultrastructure
D002210:Caprylates; D005466:Fluorocarbons; D012333:RNA, Messenger; D018160:Receptors, Cytoplasmic and Nuclear; D014157:Transcription Factors; D003577:Cytochrome P-450 Enzyme System; C023036:perfluorooctanoic acid; D010088:Oxidoreductases; D042962:Acyl-CoA Oxidase; D005982:Glutathione Transferase