Laboratory diet profoundly alters gene expression and confounds genomic analysis in mouse liver and lung.
Nutritional studies in laboratory animals have long shown that various dietary components can contribute to altered gene expression and metabolism, but diet alone has not been considered in whole animal genomic studies. In this study, global gene expression changes in mice fed either a non-purified chow or a purified diet were investigated and background metal levels in the two diets were measured by ICP-MS. C57BL/6J mice were raised for 5 weeks on either the cereal-based, non-purified LRD-5001 diet or the purified, casein-based AIN-76A diet, as part of a larger study examining the effects of low dose arsenic (As) in the diet or drinking water. Affymetrix Mouse Whole Genome 430 2.0 microarrays were used to assess gene expression changes in the liver and lung. Microarray analysis revealed that animals fed the LRD-5001 diet displayed a significantly higher hepatic expression of Phase I and II metabolism genes as well as other metabolic genes. The LRD-5001 diet masked the As-induced gene expression changes that were clearly seen in the animals fed the AIN-76A diet when each dietary group was exposed to 100 ppb As in drinking water. Trace metal analysis revealed that the LRD-5001 diet contained a mixture of inorganic and organic As at a total concentration of 390 ppb, while the AIN-76A diet contained approximately 20 ppb. These findings indicate that the use of non-purified diets may profoundly alter observable patterns of change induced by arsenic and, likely, by other experimental treatments, particularly, altering gene and protein expression.
Kozul
Courtney D
CD
Department of Pharmacology & Toxicology, Dartmouth Medical School, 7650 Remsen Building, Hanover, NH 03755-3835, United States; Center for Environmental Health Sciences, Dartmouth Medical School, Hanover, NH 03755, United States.
Nomikos
Athena P
AP
Hampton
Thomas H
TH
Warnke
Linda A
LA
Gosse
Julie A
JA
Davey
Jennifer C
JC
Thorpe
Jessica E
JE
Jackson
Brian P
BP
Ihnat
Michael A
MA
Hamilton
Joshua W
JW
D000821:Animal Feed / Q000009:adverse effects* / Q000032:analysis; D000818:Animals; D000830:Animals, Laboratory; D001151:Arsenic / Q000494:pharmacology; D005506:Food Contamination; D015870:Gene Expression / Q000187:drug effects*; D020869:Gene Expression Profiling / Q000379:methods; D016678:Genome; D008099:Liver / Q000378:metabolism / Q000502:physiology*; D008168:Lung / Q000378:metabolism / Q000502:physiology*; D008297:Male; D013058:Mass Spectrometry; D008670:Metals / Q000032:analysis / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D020411:Oligonucleotide Array Sequence Analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction
D008670:Metals; D001151:Arsenic