ROLE OF DISRUPTED GAP JUNCTIONAL INTERCELLULAR COMMUNICATION IN DETECTION AND CHARACTERIZATION OF CARCINOGENS

Results from short-term tests for carcinogens and our advanced knowled ge on cellular and molecular mechanisms of carcinogenesis strongly sug gest that carcinogens do not induce genetic changes necessarily by dir ectly interacting with DNA. Therefore, it is not surprising to see tha t many carcinogens are not detectable by available genetic toxicology tests. Thus, it has become necessary to study nongenotoxic mechanisms of carcinogenesis and to provide methods to predict those carcinogens which escape from conventional mutation tests. One possible nongenotox ic mechanism of carcinogenesis which is supported by abundant experime ntal evidence is inhibition of gap junctional intercellular communicat ion. Many, but not all, tumor-promoting agents have been shown to inhi bit the communication of cultured cells as well as in vivo. Molecular mechanisms of gap junctional intercellular communication control revea led that connexin (gap junction) genes form a family of tumor suppress or genes. Control mechanisms of expression as well as function of conn exins are vulnerable to various carcinogenic insults, notably to nonge netoxic carcinogens. Thus, studies on the role of connexins in cell gr owth and carcinogenesis may prove to be useful for establishing a mech anism-based test to detect certain types of nongenotoxic carcinogens.