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Series GSE5241 Query DataSets for GSE5241
Status Public on Jan 31, 2008
Title Liver toxicity of dichloroacetyl chloride and dichloroacetic anhydride in female MRL +/+ mice
Organism Mus musculus
Experiment type Expression profiling by array
Summary 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.
Overall design Animals: Four-week-old female MRL +/+ mice were purchased from Jackson Laboratory (Bar Harbor, ME) and housed in an animal room maintained at ~22°C and 50-60% relative humidity with a 12-h light/dark cycle. Lab chow and drinking water was provided ad libitum, and mice were acclimatized for one week before starting the treatment. Mice were injected intraperitoneally with 0.2 mmol/kg of DCAC or DCAA in 100 µl of corn oil twice weekly for six weeks. Control animals received only corn oil. Mice were sacrificed 24 h after the last treatment.
Samples: Livers from three mice per group were independently processed. The integrity of the RNA samples was tested using an Agilent 2100 Bioanalyzer and RNA 6000 LabChip® kit (Agilent Technologies, Palo Alto, CA). Only RNA samples without signs of degradation were used. Comprehensive gene expression profiles were analyzed.
Contributor(s) König R, Cai P, Guo X, Ansari G
Citation(s) 18293905
Submission date Jul 06, 2006
Last update date Feb 11, 2019
Contact name Rolf Konig
Phone (409) 747-0395
Fax (409) 772-5065
Organization name UTMB
Department Microbiology & Immunology
Street address 301 University Blvd.
City Galveston
State/province TX
ZIP/Postal code 77555-1019
Country USA
Platforms (1)
GPL1261 [Mouse430_2] Affymetrix Mouse Genome 430 2.0 Array
Samples (9)
GSM118446 MRL liver control1 11wks
GSM118507 MRL liver control2 11wks
GSM118508 MRL liver control3 11wks
BioProject PRJNA96455

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