Modulation of gene and protein expression by carbon tetrachloride in the rat liver

The gene and protein expression changes after exposure to a toxic compound might help elucidate its mechanism of action. In this paper we investigated the effect of carbon tetrachloride (CCl4) on the gene and protein expression in rat livers. Adult Wistar rats were administered CCl4, and livers were harvested 6 or 24 h thereafter. The analysis of mitochondrial proteins on 2D gels showed the upregulation of two proteins involved in stress (catalase and uricase). Among the downregulated proteins, enzymes related to the metabolism of lipids and aminoacids were affected. Additionally, alpha-2-macroglobulin and senescence marker protein, two proteins whose decrease in expression has been connected to hepatocyte damage, were decreased. Several of the upregulated genes are involved in stress response, DNA and protein damage, and repair. Genes coding for several enzymes involved in different metabolic pathways, including some P450, were downregulated in the treated animals. In conclusion, a single dose of CCl4 caused gene and protein expression changes that can be relate to its mechanism of toxicity. Results from both technologies support previous publications and provide possible new toxicity markers. However, the correlation between gene and protein expression at a given time point is less apparent, partly as a result of different regulatory mechanisms between gene and protein expression. (C) 2002 Elsevier Science (USA).