In vitro Studies of Chemical Effects on Gap-Junctional Communication: Role of Biotransformation in Toxicant Detection and Use of Assays in Risk Assessment

摘要

A correlation is emerging between the capacity of chemical substances to inhibit gap-junctional intercellular communication in vitro and their capacity to induce reproductive and developmental dysfunction, neurotoxicity and tumor promotion in vivo. A practical issue in identifying chemicals affecting gap-junctional communication in vitro is the role of metabolic products. Phenol, a weak promoter of mouse skin tumors, failed to inhibit gap-junctional communication between Chinese hamster V79 lung fibroblasts; however, five metabolites of phenol suppressed gap-junctional communication in a concentration-related manner. Sodium cyclamate, a possible promoter of bladder cancer in rats, weakly inhibited gap-junctional communication in the same assay; however, three metabolites were stronger inhibitors than sodium cyclamate. Thus, some metabolic products may show activity when parent compounds do not or may show greater activity than parent compounds.