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Series GSE26600 Query DataSets for GSE26600
Status Public on Jan 10, 2013
Title Cycad Genotoxin Methylazoxymethanol (MAM) Modulates Cellular Pathways Involved in Cancer and Neurodegenerative Disease
Organism Mus musculus
Experiment type Expression profiling by array
Summary Methylazoxymethanol (MAM), the genotoxic metabolite of the cycad azoxyglucoside cycasin, induces genetic alterations in bacteria, yeast, plants, insects and mammalian cells, but adult nerve cells are thought to be unaffected. We show that the brains of young adult mice treated with a single systemic dose of MAM display DNA damage (O6-methylguanine lesions) that peaks at 48 hours and decline to near-normal levels at 7 days post-treatment. By contrast, at this time, MAM-treated mice lacking the gene encoding the DNA repair enzyme O6-methylguanine DNA methyltransferase (MGMT), showed persistent O6-methylguanine DNA damage. The DNA damage was linked to cell-signaling pathways that are perturbed in cancer and neurodegenerative disease. These data are consistent with the established carcinogenic and developmental neurotoxic properties of MAM in rodents, and they support the proposal that cancer and neurodegeneration share common signal transduction pathways. They also strengthen the hypothesis that early life exposure to the MAM glucoside cycasin has an etiological association with a declining, prototypical neurodegenerative disease seen in Guam, Japan, and New Guinea populations that formerly used the neurotoxic cycad plant for medicine and/or food. Exposure to environmental genotoxins may have relevance to the etiology of related tauopathies, notably, Alzheimer’s disease, as well as cancer.
Overall design Mouse brains from eleven-week-old male C57BL6 wild-type and Mgmt-/- mice were exposed to either MAM or Vehicle for 6 hr, 24 hr, 48 hr, 168 hr. Five or six mice per group for a total of 94 mice.
Contributor(s) Beyer RP, Bammler TK, Churchwell M, Cranson A, Crawford A, Doerge D, Fry RC, Kisby G, Lasarev M, Meira LB, Palmer VS, Ren X, Sullivan RC, Crawford A, Kavanagh TJ, Samson LD, Zarbl H, Spencer PS
Citation(s) 21731631
Submission date Jan 12, 2011
Last update date Feb 11, 2019
Contact name James William MacDonald
Organization name University of Washington
Department Environmental and Occupational Health Sciences
Street address 4225 Roosevelt Way NE
City Seattle
State/province WA
ZIP/Postal code 98105-6099
Country USA
Platforms (1)
GPL1261 [Mouse430_2] Affymetrix Mouse Genome 430 2.0 Array
Samples (94)
GSM654777 WT.VEH.6.101
GSM654778 WT.VEH.6.103
GSM654779 WT.VEH.6.105
BioProject PRJNA136203

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Supplementary file Size Download File type/resource
GSE26600_RAW.tar 564.6 Mb (http)(custom) TAR (of CEL)
Raw data provided as supplementary file
Processed data included within Sample table

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