Unknown,Transcriptomics,Genomics,Proteomics

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Transcription profiling of mouse skin from K6/ODC animals response to folate deficient diets reveals folate deficiency enhances arsenic effects

ABSTRACT: We demonstrate that expression of key markers of keratinocyte differentiation is suppressed by exposure to sodium arsenite. Folate deficiency exacerbates this effect. In addition, cancer-related cell movement genes, and growth and proliferation genes are altered. Several redox-sensitive transcription factors are implicated in mediating these gene expression changes due to arsenic treatment and folate deficiency. Experiment Overall Design: K6/ODC mice were maintained on either a folate deficient or folate sufficient diet and exposed to 0, 1, or 10 ppm sodium arsenite in the drinking water for 30 days. Total RNA was isolated from skin samples and gene expression analyzed using Affymetrix Mouse 430 2.0 GeneChips. Data from 24 samples, with four mice in each of the six treatment groups, were analyzed.

ORGANISM(S): Mus musculus

SUBMITTER: Gail Nelson

PROVIDER: E-GEOD-8733 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Folate deficiency enhances arsenic effects on expression of genes involved in epidermal differentiation in transgenic K6/ODC mouse skin.

Nelson Gail M GM Ahlborn Gene J GJ Delker Don A DA Kitchin Kirk T KT O'Brien Thomas G TG Chen Yan Y Kohan Michael J MJ Roop Barbara C BC Ward William O WO Allen James W JW

Toxicology 20070901 3

Chronic arsenic exposure in humans is associated with cancers of the skin, lung, bladder and other tissues. There is evidence that folate deficiency may increase susceptibility to arsenic effects, including skin lesions. K6/ODC mice develop skin tumors when exposed to 10ppm sodium arsenite for 5 months. In the current study, K6/ODC mice maintained on either a folate deficient or folate sufficient diet were exposed to 0, 1, or 10ppm sodium arsenite in the drinking water for 30 days. Total RNA was ...[more]

PMID: 17928125

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Project description:Folate deficiency, arsenic exposure, and gamma-IR are known developmental toxicants and have carcinogenic effects. The mechanism by which IR is known, but the effect of arsenic or folate deficiency remains unclear. Their effect may be mediated by epigenetic alterations, leading to miRNA expression changes, and this experiment examined this hypothesis We used microarrays to detail the miRNA expression profiles of TK6 cells treated with 2 uM sodium arsenite for 6 days, folate-deficient media for 6 days, or 2.5 Gy IR exposure either acutely at 4 hours post exposure or long-term at 6 days post exposure, as well as requiste controls, all in biological triplicate. Keywords: exposure differences TK6, were cultured in standard RPMI 1640 (Invitrogen Inc., Gaithersburg, MD) or folate-deficient RPMI 1640 (Invitrogen). Growth media was supplemented with 10% fetal bovine serum (Invitrogen) and 1% penicillin-streptomycin; dialyzed fetal bovine serum (Invitrogen) was added to the folate-deficient medium in order to eliminate folic acid in the serum. For controls, folate-deficiency, arsenic exposure, and 6-day ?-IR exposure groups, 106 cells were diluted into 50ml of appropriate growth media. For the 4-hour post-?-IR exposure group, 107 cells were diluted into 50ml of growth media. For the arsenic exposed group, sodium arsenite was added to the media to a concentration of 2 ?M. For the ?-IR exposure groups, cells were diluted and allowed to incubate for 4 hours prior to irradiation treatment, and were exposed at a dose rate of 86.76 rad/min to a final dose of 2.5 Gy using a Philips MGC-40 X-ray source. Following exposure, cells were returned to the incubator. After fours hours, the short-term post-??-IR exposure group was collected for RNA isolation, as well as a mock (control) group. All experimental and control conditions were performed in triplicate. For all other groups, cells were cultured for 6 days, with the media changed and renewed, with the appropriate treatment, on day 3.

Dataset Information

Transcription profiling of mouse skin from K6/ODC animals response to folate deficient diets reveals folate deficiency enhances arsenic effects

Publications

Folate deficiency enhances arsenic effects on expression of genes involved in epidermal differentiation in transgenic K6/ODC mouse skin.

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