Triglyceride accumulation in long-term cultures of adult rat hepatocytes by chronic exposure to Aroclor 1254
- Instituto Politecnico Nacional, Mexico City (Mexico)
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 mytomicin C-treated 3T3 cells and exposed for 2 wk to Aroclor 1254 concentrations ranging from 0.01 to 20 {mu}g/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 ({sup 14}C)acetic and ({sup 14}C)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 ({sup 14}C)acetic acid was slightly inhibited by Aroclor 1254, but that from ({sup 14}C)oleic acid was increased, specially for TF (37%). The secretion of total lipids and TG was 2.1- and 2.7-fold lower, respectively, in the cultures treated with 20 {mu}g/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 ({sup 3}H)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 {mu}g/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).
- OSTI ID:
- 6967495
- Journal Information:
- Journal of Toxicology and Environmental Health; (USA), Vol. 26:3; ISSN 0098-4108
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
59 BASIC BIOLOGICAL SCIENCES
CHLORINATED AROMATIC HYDROCARBONS
TOXICITY
LIPIDS
METABOLISM
LIVER CELLS
MORPHOLOGICAL CHANGES
BIOCHEMICAL REACTION KINETICS
CARBON 14 COMPOUNDS
CHRONIC EXPOSURE
RATS
TRACER TECHNIQUES
ANIMAL CELLS
ANIMALS
AROMATICS
HALOGENATED AROMATIC HYDROCARBONS
ISOTOPE APPLICATIONS
KINETICS
LABELLED COMPOUNDS
MAMMALS
ORGANIC CHLORINE COMPOUNDS
ORGANIC COMPOUNDS
ORGANIC HALOGEN COMPOUNDS
REACTION KINETICS
RODENTS
SOMATIC CELLS
VERTEBRATES
560300* - Chemicals Metabolism & Toxicology
550201 - Biochemistry- Tracer Techniques