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Use of Primary Cultures of Adult Rat Hepatocytes to Study the Mode of Action of the Peroxisome Proliferator Nafenopin

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Peroxisomes in Biology and Medicine

Part of the book series: Proceedings in Life Sciences ((LIFE SCIENCES))

Abstract

The increasing number of reports on various hepatic functions in primary cultures of adult rat hepatocytes is a reflection of the usefulness of such culture systems. The activity of many hepatic enzymes including several of peroxisomal origin decreases during a few days of culture. However, peroxisomal activities may be increased by addition of nafenopin to the culture medium. This increase correlated with a proliferation of the peroxisomal compartment observed morphologically. Nafenopin treatment also induced a wave of RNA synthesis and DNA synthesis; the level of cytochrome P 450 was increased and the spontaneous appearance of γ-glutamyl transpeptidase was delayed. Further studies indicated that DNA-synthesis and peroxisomal proliferation could be stimulated independently. Moreover, when a range of peroxisome proliferators were studied it was found that the mitotic response could not be predicted from the effect upon the peroxisomal compartment.

Recent studies using hepatocytes in long-term culture in the presence of 2% DMSO indicate that nafenopin-treated cultures have a survival advantage over control cultures. Further investigation of this phenomenon may aid our understanding of modifications made to the cellular differentiation programme by nafenopin which in tum will contribute to our knowledge of the mechanism by which peroxisome proliferators induce hepatocellular tumours.

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© 1987 Springer-Verlag Berlin Heidelberg

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Bieri, F., Muakkassah-Kelly, S., Waechter, F., Stäubli, W., Bentley, P. (1987). Use of Primary Cultures of Adult Rat Hepatocytes to Study the Mode of Action of the Peroxisome Proliferator Nafenopin. In: Fahimi, H.D., Sies, H. (eds) Peroxisomes in Biology and Medicine. Proceedings in Life Sciences. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-71325-5_29

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  • DOI: https://doi.org/10.1007/978-3-642-71325-5_29

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-642-71327-9

  • Online ISBN: 978-3-642-71325-5

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