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Models and methods for in vitro testing of hepatic gap junctional communication

Michaël Maes1, Sara Crespo Yanguas1, Joost Willebrords1

  • 1Department of In Vitro Toxicology and Dermato-Cosmetology, Vrije Universiteit Brussel, Laarbeeklaan 103, B-1090 Brussels, Belgium.

Toxicology in Vitro : an International Journal Published in Association with BIBRA
|October 1, 2015
PubMed

Insights

Liver cell gap junctions, primarily connexin32, are disrupted by toxins. Their inhibition indicates non-genotoxic hepatocarcinogenicity, making it a key biomarker for liver toxicity testing.

Area of Science:

  • Hepatocellular biology and toxicology
  • Cellular communication and gap junctions

Background:

  • Hepatocellular gap junctions, mainly connexin32, regulate liver cell life cycles.
  • These junctions are disrupted by impaired homeostatic balance, such as during liver toxicity.
  • Tumor promoters and epigenetic carcinogens specifically target hepatic gap junctions.

Purpose of the Study:

  • To establish connexin32-based gap junction inhibition assays for routine in vitro testing.
  • To identify reliable cellular systems and techniques for probing gap junction activity in liver toxicity assessment.

Main Methods:

  • Discussion of cellular models expressing in vivo-like levels of gap junctions.
  • Review of appropriate techniques for assessing gap junction activity and inhibition.
  • Focus on connexin32-based gap junctions for assay development.

Main Results:

  • Inhibition of gap junction functionality serves as a reliable indicator for detecting non-genotoxic hepatocarcinogenicity.
  • The study discusses models and methods crucial for developing robust in vitro liver toxicity assays.

Conclusions:

  • Connexin32-based gap junction inhibition assays are suitable for in vitro detection of non-genotoxic hepatocarcinogenicity.
  • Development of reliable assays requires specific cellular systems and techniques to probe gap junction activity.
Keywords:
ConnexinGap junctionIn vitro modelIntercellular communicationLiverNongenotoxic carcinogen

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