Disruption of gap junctions in toxicity and carcinogenicity.

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.