Targeting gap junctional intercellular communication by hepatocarcinogenic compounds

ABSTRACT

Gap junctions in liver, as in other organs, play a critical role in tissue homeostasis. Inherently, these cellular constituents are major targets for systemic toxicity and diseases, including cancer. This review provides an overview of chemicals that compromise liver gap junctions, in particular biological toxins, organic solvents, pesticides, pharmaceuticals, peroxides, metals and phthalates. The focus in this review is placed upon the mechanistic scenarios that underlie these adverse effects. Further, the potential use of gap junctional activity as an in vitro biomarker to identify non-genotoxic hepatocarcinogenic chemicals is discussed.

KEYWORDS:

• Connexin
• gap junction intercellular communication
• hepatocarcinogenicity
• non-genotoxic carcinogenic compounds
• risk assessment
• hemichannel
• in vivo
• in vitro

List of abbreviations

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Conflicts of interest

The authors report no conflicts of interest.

Additional information

Funding

This study was financially supported by the Fund for Scientific Research-Flanders [FWO Vlaanderen Grants G009514N and G010214N], the Fundação de Amparo à Pesquisa do Estado de São Paulo [FAPESP-FWO Grant 18/10953-9], the University Hospital of the Vrije Universiteit Brussel-Belgium (Willy Gepts Fonds UZ-Brussel) and the Center for Alternatives to Animal Testing at Johns Hopkins University-USA [Grant 2018-13].