Role of connexins in chemical carcinogenesis
Carcinogenic substances have conventionally been divided into two categories according to their presumed mechanism of action: genotoxic or non-genotoxic. Many chemicals that cause cancer in animal studies are negative in genotoxicity assays, suggesting that these chemicals may act in a non-genotoxic manner. It is a major challenge to understand how non-genotoxic carcinogens function and to develop methods to detect such compounds in the environment. Many carcinogenic chemicals inhibit gap junction channels. The ability of chemicals to inhibit gap junctional intercellular communication is associated with their carcinogenicity, but not with their genotoxicity. We are investigating the molecular mechanisms by which chemical carcinogens inactivate gap junction channels.