Exploring the relationship between the inhibition of gap junctional intercellular communication and other biological phenomena.

The mechanistic relationship of the inhibition of gap junctional intercellular communication (GJIC) to other toxicological phenomena was explored using a recently developed method that models the properties of a large population of molecules chosen to represent the 'universe of chemicals'. The analyses indicate that inhibition of GJIC is strongly linked to the carcinogenic process in rodents, to cellular but not systemic toxicity, to biological phenomena that may involve inflammatory processes and to development effects. The inhibition of GJIC appears not to be associated with genotoxic mechanisms. With respect to cancer causation, integration of the analyses suggests that inhibition of GJIC is involved in non-genotoxic cancer induction or in the non-genotoxic phases of the carcinogenic process (such as inflammation, cell toxicity, cell proliferation, inhibition of cell differentiation and apoptosis).