The Role of Intercellular Communication in the Evaluation in vitro/in vivo Toxicity Testing of Chemicals,
MICHIGAN STATE UNIV EAST LANSING
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Several of the pressing scientific challenges in the filed of environmental toxicology are to understand the basic mechanisms of chemically-induced toxic substances and of the design, interpretation, and extrapolation of data from non-human bioassay systems to the human situation. The objective is to offer a new paradigm, namely the idea that cytotoxic and epigenetic effects of chemicals can contribute to many toxic endpoints in human beings. We will speculate that the disruption of calcium homeostasis by a wide variety of chemicals and the conditions of their use might provide an unification of mechanisms leading to either cytotoxicity or epigenetic changes. Depending on the conditions, the effects of this disruption, a pleiotropy of diseases might result, namely, embryotoxicity, teratogenesis, tumor promotion, immune modulation, neurotoxicity, and preproductive dysfunction. In summary, there are at least three biological endpoints at the cell level which chemicals can influence - mutations, cell death, and epigenetic changes.