Triglyceride accumulation in long-term cultures of adult rat hepatocytes by chronic exposure to Aroclor 1254.
The effect of chronic exposure to micromolar concentrations of Aroclor 1254 (Aro) on the hepatic lipid metabolism was studied in long-term cultures of adult rat hepatocytes. Hepatocytes were cocultivated with mitomycin C-treated 3T3 cells and exposed for 2 wk to Aroclor 1254 concentrations ranging from 0.01 to 20 micrograms/ml. The Aro-exposed cultures showed intracytoplasmic lipid droplets and a maximum increase of 55% in the triglyceride (TG) content and of 4.4-fold in the cytochrome P-450 content. Labeling studies with [14C]acetic and [14C]oleic acid showed no changes in the uptake of fatty acid and TG precursors by the Aro-treated cultures; the synthesis of cellular lipids from [14C]acetic acid was slightly inhibited by Aroclor 1254, but that from [14C]oleic acid was increased, specially for TG (37%). The secretion of total lipids and TG was 2.1- and 2.7-fold lower, respectively, in the cultures treated with 20 micrograms/ml of Aroclor 1254, resulting in an increase of 1.9-fold in the intracellular content of TG. The synthesis of cellular proteins labeled with [3H]leucine was unchanged in the Aro-treated cultures, but the secretion of exportable proteins was 1.7-fold lower in the cultures treated with 20 micrograms/ml of Aroclor 1254. Our results showed that long-term exposure to in vivo relevant concentrations of Aroclor 1254 produced morphological and biochemical changes in cultured hepatocytes, like those described in vivo, and intracellular TG accumulation due mostly to impaired secretion of TG by the hepatocytes. Our results also suggest that this culture system could be useful for the screening of toxic agents producing fatty liver and the study of the involved mechanism(s).
Mendoza-Figueroa
T
T
Department of Pharmacology and Toxicology, Instituto Politécnico Nacional, Mexico City, Mexico.
Hernández
A
A
López
M L
ML
D000085:Acetates / Q000378:metabolism; D019342:Acetic Acid; D000818:Animals; D001140:Aroclors / Q000633:toxicity*; D002478:Cells, Cultured; D002855:Chromatography, Thin Layer; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D050356:Lipid Metabolism; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D008297:Male; D019301:Oleic Acid; D009829:Oleic Acids / Q000378:metabolism; D011078:Polychlorinated Biphenyls / Q000633:toxicity*; D011506:Proteins / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D013997:Time Factors; D014280:Triglycerides / Q000378:metabolism*
D000085:Acetates; D001140:Aroclors; D009829:Oleic Acids; D011506:Proteins; D014280:Triglycerides; D019301:Oleic Acid; D003577:Cytochrome P-450 Enzyme System; D011078:Polychlorinated Biphenyls; D019342:Acetic Acid