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Toxicological Sciences 71, 146-153 (2003)
Copyright © 2003 by the Society of Toxicology

FORUM

Disruption of Gap Junctions in Toxicity and Carcinogenicity

J. Kevin Chipman1, Angela Mally and Gareth O. Edwards

School of Biosciences, The University of Birmingham, Edgbaston, Birmingham B15 2TT, United Kingdom

Although the specific role of connexin-mediated gap junctional intercellular communication in the control of cell homeostasis, proliferation, and death are still not clear, several lines of evidence support these roles. The disturbance of this communication, through multiple mechanisms, may in the short term be a protective mechanism to limit the spread of toxicity in a tissue following chemical or radiation damage. However, sustained downregulation confers a loss of tumor-suppressive action. Consequently, connexin dysfunction has been associated with both the action of many carcinogens and being a feature of cancer per se. Connexins offer not only a target for cancer chemoprevention but also for exploitation in chemotherapy through the "bystander" effect.

Key Words: connexin; gap junction; carcinogenesis; bystander; intercellular communication.


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