Liver toxicity of dichloroacetyl chloride and dichloroacetic anhydride in female MRL +/+ mice

ABSTRACT: Dichloroacetyl chloride (DCAC) is a metabolic intermediate of trichloroethene (TCE), an industrial chemical and ubiquitous environmental contaminant. TCE and its metabolites have been implicated in the induction of organ-specific and systemic autoimmunity, in the acceleration of autoimmune responses, and in the development of liver toxicity. In humans, effects of environmental toxicants are often multifactorial and detected only after long-term exposure. Therefore, we developed a small-animal model to determine mechanisms by which DCAC and related acylating agents affect liver disease. Autoimmune-prone female MRL +/+ mice were injected i.p. with 0.2 mmole/kg of DCAC or the acylating agent dichloroacetic anhydride (DCAA) in corn oil twice weekly for six weeks. We then determined changes in the liver transcriptome using microarray gene expression analysis. After exposure to DCAC or DCAA, we observed changes in liver gene expression consistent with inflammatory processes. Both toxicants up-regulated expression of acute phase response and inflammatory genes. Further, metallothionein genes were strongly up-regulated, indicating effects of the toxicants on zinc ion homeostasis and stress responses. In addition, DCAC and DCAA induced up-regulation of several genes indicative of tumorogenesis. Microarray gene expression analysis using a restricted set of genes could be a valuable tool to screen for early changes in liver function following suspected exposure to environmental toxicants. Keywords: Response to acylating agents; inflammatory response; disease state analysis.

ORGANISM(S): Mus musculus

PROVIDER: GSE5241 | GEO | 2008/01/31

SECONDARY ACCESSION(S): PRJNA96455

REPOSITORIES: GEO