© 1997 by The Society for Integrative and Comparative Biology
Evaluating Intracellular Signaling Pathways as Biomarkers for Environmental Contaminant Exposures1
Marine Biomedical and Environmental Sciences, Department of Microbiology & Immunology, The Medical University of South Carolina 221 Fort Johnson Road, Charleston, South Carolina 29412
Correspondence: 2 E-mail: burnetkg{at}musc.edu
The number of biomarkers being evaluated as environmental indicators continues to increase even as proposed assessments expand in complexity. One key to a rational consolidation may lie in clearly identifying and characterizing those biochemical pathways shared among many biomarkers which are sensitive to environmental perturbation. Recent studies suggest that signal transduction pathways which are common to many cell types and species may provide multiple targets for the toxic effects of heavy metals. Such intracellular communication pathways might provide a useful framework for understanding hormetic effects and for predicting responses to complex contaminant mixtures. Preliminary in vitro experiments tested the effects of mercuric chloride (HgCl2) and cadmium chloride (CdCl2) on signal transduction in cells of the teleost immune system. Concentrations of inorganic mercury 
µM suppressed DNA synthesis and induced rapid influx of radiolabelled calcium within ten minutes as well as tyrosine phosphorylation of numerous cellular proteins within one minute. Lower concentrations (0.1 – 1 µM) of HgCl2 which activated cell growth also induced a slow rise over two minutes in intracellular calcium in cells loaded with the calcium indicator dye, fura-2, but did not produce detectable tyrosine phosphorylation of leukocyte proteins. Although CdCl2 >10 µM also suppressed DNA synthesis, this environmental metal failed to activate cell growth or to induce tyrosine kinase activity at any concentration tested. Future experiments will assess how cells which are exposed to both metals integrate these mixed signals. This approach may provide a means of predicting cellular responses to multiple contaminants over broad dose ranges