Exposure to Cobalt Causes Transcriptomic and Proteomic Changes in Two Rat Liver Derived Cell Lines

Cobalt is a transition group metal present in trace amounts in the human diet, but in larger doses it can be acutely toxic or cause adverse health effects in chronic exposures. Its use in many industrial processes and alloys worldwide presents opportunities for occupational exposures, including military personnel. While the toxic effects of cobalt have been widely studied, the exact mechanisms of toxicity remain unclear. In order to further elucidate these mechanisms and identify potential biomarkers of exposure or effect, we exposed two rat liver-derived cell lines, H4-II-E-C3 and MH1C1, to two concentrations of cobalt chloride. We examined changes in gene expression using DNA microarrays in both cell lines and examined changes in cytoplasmic protein abundance in MH1C1 cells using mass spectrometry. We chose to closely examine differentially expressed genes and proteins changing in abundance in both cell lines in order to remove cell line specific effects. We identified enriched pathways, networks, and biological functions using commercial bioinformatic tools and manual annotation. Many of the genes, proteins, and pathways modulated by exposure to cobalt appear to be due to an induction of a hypoxic-like response and oxidative stress. Genes that may be differentially expressed due to a hypoxic-like response are involved in Hif-1α signaling, glycolysis, gluconeogenesis, and other energy metabolism related processes. Gene expression changes linked to oxidative stress are also known to be involved in the NRF2-mediated response, protein degradation, and glutathione production. Using microarray and mass spectrometry analysis, we were able to identify modulated genes and proteins, further elucidate the mechanisms of toxicity of cobalt, and identify biomarkers of exposure and effect in vitro, thus providing targets for focused in vivo studies.     

Environmental Chemicals and Nervous System Dysfunction

Selected examples of associations between nervous system diseases and exposures to occupational and environmental chemicals have been reviewed. Recent outbreaks of human neurotoxicity from both wellknown and previously unknown toxicants reemphasize the need for the medical community to give increased attention to chemical causes of nervous system dysfunction.     

Chemical Contamination of California Drinking Water

Drinking water contamination by toxic chemicals has become widely recognized as a public health concern since the discovery of 1,2-dibromo-3-chloropropane in California''s Central Valley in 1979. Increased monitoring since then has shown that other pesticides and industrial chemicals are present in drinking water. Contaminants of drinking water also include naturally occurring substances such as asbestos and even the by-products of water chlorination. Public water systems, commercially bottled and vended water and mineral water are regulated, and California is also taking measures to prevent water pollution by chemicals through various new laws and programs.