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Series GSE32102 Query DataSets for GSE32102
Status Public on Sep 15, 2011
Title Arsenate Sub-chronic Drinking Water Study
Organism Mus musculus
Experiment type Expression profiling by array
Summary Concentration- and time-dependent genomic changes in the mouse urinary bladder following exposure to arsenate in drinking water for up to twelve weeks.

Inorganic arsenic (Asi) is a known human bladder carcinogen. The objective of this study was to examine the concentration dependence of the genomic response to Asi in the urinary bladders of mice. C57BL/6J mice were exposed for 1 or 12 weeks to arsenate in drinking water at concentrations of 0.5, 2, 10, and 50 mg As/L. Urinary bladders were analyzed using gene expression microarrays. A consistent reversal was observed in the direction of gene expression change: from predominantly decreased expression at 1 week to predominantly increased expression at 12 weeks. These results are consistent with evidence from in vitro studies of an acute adaptive response that is suppressed on longer exposure due to down-regulation of Fos. Pathways with the highest enrichment in gene expression changes were associated with epithelial-to-mesenchymal transition, inflammation, and proliferation. Benchmark dose (BMD) analysis determined that the lowest median BMD values for pathways were above 5 mg As/L, despite the fact that pathway enrichment was observed at the 0.5 mg As/L exposure concentration. This disparity may result from the non-monotonic nature of the concentration-responses for the expression changes of a number of genes, as evidenced by the much fewer gene expression changes at 2 mg As/L compared to lower or higher concentrations. Pathway categories with concentration-related gene expression changes included cellular morphogenesis, inflammation, apoptosis/survival, cell cycle control, and DNA damage response. The results of this study provide evidence of a concentration-dependent transition in the mode of action for the subchronic effects of Asi in mouse bladder cells in the vicinity of 2 mg Asi/L.
Overall design Female C57Bl/J mice will be exposed to COLD Arsenate in drinking water. One week interium sac on 7/18/06. 100 samples including liver, lung, kidney and bladder. Bladder will be analyzed with microarrays, 24 samples. Twelve week terminal sac on 10/05/06. 75 total samples including lung, kidney, and bladder. Bladdler will be analyzed by microarray, 25 samples. Drinking water containing As will be prepared weekly with monitoring to determine amount used by mice. Following tissues will be available for genomic study: Bladder, liver, lung, and kidney.
Contributor(s) Clewell HJ, Thomas RS, Kenyon EM, Hughes MF, Adair BM, Gentry PR, Yager JW
Citation(s) 21795629
Submission date Sep 13, 2011
Last update date Feb 11, 2019
Contact name Harvey Clewell
Organization name The Hamner Institutes for Health Sciences
Street address 6 Davis Drive
City RTP
State/province NC
ZIP/Postal code 27709
Country USA
Platforms (1)
GPL1261 [Mouse430_2] Affymetrix Mouse Genome 430 2.0 Array
Samples (49)
GSM795653 HC_05_12wk_7-1
GSM795654 HC_05_12wk_7-2
GSM795655 HC_05_12wk_7-3
BioProject PRJNA147543

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Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE32102_RAW.tar 298.2 Mb (http)(custom) TAR (of CEL)
Raw data provided as supplementary file
Processed data included within Sample table

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