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Peroxisome proliferators induce apoptosis and decrease DNA synthesis in hepatoma cell lines.

V Goll1, C Viollon-Abadie, L Nicod

  • 1Laboratoire de Biologie Cellulaire, Faculté de Médecine et de Pharmacie, Besançon, France.

Human & Experimental Toxicology
|July 13, 2000
PubMed
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Peroxisome proliferators (PPs) increased enzyme activity and apoptosis in rat liver cells but had varied effects on human liver cells. These findings contrast with previous studies on primary hepatocytes.

Area of Science:

  • Hepatology
  • Toxicology
  • Cell Biology

Background:

  • Peroxisome proliferators (PPs) are compounds known to affect liver cell function.
  • Previous studies indicated PPs alter enzyme activity, apoptosis, and DNA synthesis in primary hepatocytes.

Purpose of the Study:

  • To investigate the impact of various PPs on peroxisomal enzyme activity, apoptosis, and DNA synthesis in rat FaO and human HepG2 hepatoma cell lines.
  • To compare the cellular responses in hepatoma cell lines with those observed in primary hepatocyte cultures.

Main Methods:

  • Treatment of rat FaO and human HepG2 hepatoma cell lines with PPs (clofibric acid, bezafibrate, ciprofibrate, nafenopin, DEHP) at 250 microM for 48 or 72 hours.
  • Assay of peroxisomal enzyme activities, apoptosis markers, and DNA synthesis.

Related Experiment Videos

  • Evaluation of effects on both growing and confluent cell cultures.
  • Main Results:

    • PPs increased peroxisomal enzyme activities in rat FaO cells but not in human HepG2 cells.
    • PPs strongly induced apoptosis in FaO cells, with some exceptions for DEHP and NAFE regarding TGFbeta-induced apoptosis in confluent cultures.
    • PPs decreased DNA synthesis in FaO cells and growing HepG2 cells, while CLO, CIPRO, and NAFE induced apoptosis in confluent HepG2 cultures.

    Conclusions:

    • Hepatoma cell lines exhibit differential responses to PPs compared to primary hepatocytes.
    • PPs demonstrate cell-type-specific effects on peroxisomal activity, apoptosis, and DNA synthesis.
    • The study highlights the importance of cell context in understanding PP-induced toxicity.