Gene expression profiling of low selenium status in the mouse intestine: transcriptional activation of genes linked to DNA damage, cell cycle control and oxidative stress.
The essential trace mineral selenium (Se) has been shown previously to inhibit intestinal, prostate, lung and liver tumor development and associated mortality in both experimental animals and humans. Although Se is likely to be one of the most powerful cancer chemopreventive agents in the human diet, its mechanism of action is unknown. To better understand the biological consequences of alterations in Se status, the gene expression profile associated with low Se status in the intestine of C57Bl/6J mice was analyzed. Mice were fed either a high fat (14%), torula yeast-based, Se-deficient diet (<0.01 mg/kg) or the same diet supplemented with a high level of dietary Se (1 mg/kg, as seleno-L-methionine) for 90 d. Use of high density oligonucleotide arrays representing 6347 genes revealed that low Se status results in a differential gene expression pattern indicative of activation of genes involved in DNA damage, oxidative stress and cell cycle control, and a decrease in the expression of genes involved in detoxification. These results suggest that suboptimal intake of a single trace mineral can have broad effects on gene expression patterns, providing a framework for understanding the multiple beneficial effects of Se in cancer chemoprevention and human health.
Rao
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Department of Genetics, University of Wisconsin-Madison, Madison, WI 53706, USA.
Puschner
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B
Prolla
T A
TA
D000818:Animals; D016588:Anticarcinogenic Agents; D002453:Cell Cycle / Q000235:genetics*; D004249:DNA Damage / Q000235:genetics*; D004032:Diet; D015870:Gene Expression; D007413:Intestinal Mucosa / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D009752:Nutritional Status; D020411:Oligonucleotide Array Sequence Analysis; D018384:Oxidative Stress / Q000235:genetics*; D011506:Proteins / Q000235:genetics; D012643:Selenium / Q000008:administration & dosage / Q000172:deficiency / Q000502:physiology*; D051140:Selenoproteins; D014158:Transcription, Genetic
D016588:Anticarcinogenic Agents; D011506:Proteins; D051140:Selenoproteins; D012643:Selenium