Genomics

Dataset Information

0

Cycad Genotoxin Methylazoxymethanol (MAM) Modulates Cellular Pathways Involved in Cancer and Neurodegenerative Disease


ABSTRACT: 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.

ORGANISM(S): Mus musculus

PROVIDER: GSE26600 | GEO | 2013/01/10

SECONDARY ACCESSION(S): PRJNA136203

REPOSITORIES: GEO

Similar Datasets

| E-GEOD-26600 | biostudies-arrayexpress
2022-04-01 | PXD028683 | Pride
2023-12-12 | GSE249155 | GEO
2019-01-09 | GSE108925 | GEO
| E-GEOD-5093 | biostudies-arrayexpress
2006-08-17 | GSE5093 | GEO
2024-01-01 | GSE239403 | GEO
2017-12-15 | GSE108098 | GEO
2019-10-16 | GSE138853 | GEO
2024-01-23 | GSE231419 | GEO