The Role of Chemical Inhibition of Gap-Junctional Intercellular Communication in Toxicology
Abstract
The overall goal of this grant has been to study the mechanisms by which non-genotoxic chemicals act. Specifically, the working hypothesis has been that chemical modulation of gap junctions could lead to many toxic endpoints, such as teratogenesis, tumor promotion, immune-reproductive- and neuro- toxicities. To test this hypothesis, we set up several aims: a) to develop new methods to measures to measure gap junction function (Fluorescence Recovery After Photo-bleaching and scrape-loading/dye transfer); b) to test if several known model non-genotoxic chemicals inhibit intercellular communication in several cell types; and c) to study the biochemical mechanisms by which various chemicals inhibit intercellular communication. Results of this 3 year study have produced a) three new validated in vitro methods to measure gap junction; b) produced overwhelming evidence that known non-genotoxic teratogens, tumor promoters, neuro-, and reproductive-toxicants can inhibit gap junction function; c) evidence suggesting several biochemical mechanisms by which these chemicals act; and d) helped develop a new theoretical framework for a biologically-based risk assessment model system.
Document Details
- Document Type
- Technical Report
- Publication Date
- Mar 01, 1989
- Accession Number
- ADA207130
Entities
People
- James E. Trosko
Organizations
- Michigan State University