Evaluating the transcriptomic and metabolic profile of mice exposed to source drinking water.

Transcriptomic and metabonomic methods were used to investigate mice's responses to drinking source water (DSW) exposure. After mice were fed with DSW for 90 days, hepatic transcriptome was characterized by microarray and serum metabonome were determined by (1)H nuclear magnetic resonance (NMR) spectroscopy. A total of 243 differentially expressed genes (DEGs) were identified, among which 141 genes were up-regulated and 102 genes were down-regulated. Metabonomics revealed significant changes in concentrations of creatine, pyruvate, glutamine, lysine, choline, acetate, lipids, taurine, and trimethylamine oxide. Four biological pathways were identified by Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis where both gene expression and metabolite concentrations were altered in response to DSW exposure. These results highlight the significance of combined use of transcriptomic and metabonomic approaches in evaluating potential health risk induced by DSW contaminated with various hazardous materials.

[1]  Richard D Beger,et al.  Metabolomics approaches for discovering biomarkers of drug-induced hepatotoxicity and nephrotoxicity. , 2010, Toxicology and applied pharmacology.

[2]  A. Santra,et al.  Arsenic induces apoptosis in mouse liver is mitochondria dependent and is abrogated by N-acetylcysteine. , 2007, Toxicology and applied pharmacology.

[3]  Yan Zhang,et al.  A metabonomic analysis on health effects of drinking water on male mice (Mus musculus). , 2011, Journal of hazardous materials.

[4]  M. Breyer,et al.  Peroxisome proliferator-activated receptors (PPARs): novel therapeutic targets in renal disease. , 2001, Kidney international.

[5]  Jia Cao,et al.  Ovotoxicity and PPAR-mediated aromatase downregulation in female Sprague-Dawley rats following combined oral exposure to benzo[a]pyrene and di-(2-ethylhexyl) phthalate. , 2010, Toxicology letters.

[6]  Mark R Viant,et al.  Direct sampling of organisms from the field and knowledge of their phenotype: key recommendations for environmental metabolomics. , 2007, Environmental science & technology.

[7]  Xu-xiang Zhang,et al.  Gene expression profiles in liver of mouse after chronic exposure to drinking water , 2009, Journal of applied toxicology : JAT.

[8]  E. Tai,et al.  A natural polymorphism in peroxisome proliferator-activated receptor-alpha hinge region attenuates transcription due to defective release of nuclear receptor corepressor from chromatin. , 2008, Molecular endocrinology.

[9]  Zhenyao Shen,et al.  Distribution and speciation of heavy metals in sediments from the mainstream, tributaries, and lakes of the Yangtze River catchment of Wuhan, China. , 2009, Journal of hazardous materials.

[10]  Andreas Kortenkamp,et al.  Cross-talk between non-genomic and genomic signalling pathways--distinct effect profiles of environmental estrogens. , 2010, Toxicology and applied pharmacology.

[11]  A. Kong,et al.  Induction of phase I, II and III drug metabolism/transport by xenobiotics , 2005, Archives of pharmacal research.

[12]  X. Qian,et al.  Genotoxicity of organic pollutants in source of drinking water on microalga Euglena gracilis , 2009, Ecotoxicology.

[13]  P. Mehdipour,et al.  Association between the FABP2 Ala54Thr, PPARα Leu162/Val, and PPARα intron7 polymorphisms and blood lipids ApoB and ApoCIII in hypertriglyceridemic subjects in Tehran. , 2009, Journal of clinical lipidology.

[14]  Shiyuan Xu,et al.  Identification of the sources of polycyclic aromatic hydrocarbons based on molecular and isotopic characterization from the Yangtze estuarine and nearby coastal areas , 2010 .

[15]  Oliver A.H. Jones,et al.  A metabolomics based approach to assessing the toxicity of the polyaromatic hydrocarbon pyrene to the earthworm Lumbricus rubellus. , 2008, Chemosphere.

[16]  May R Berenbaum,et al.  Molecular mechanisms of metabolic resistance to synthetic and natural xenobiotics. , 2007, Annual review of entomology.

[17]  A. Viarengo,et al.  Mixture Toxicity Assessment of Nickel and Chlorpyrifos in the Sea Bass Dicentrarchus labrax , 2011, Archives of environmental contamination and toxicology.

[18]  Pawel Rostkowski,et al.  Profiles and some initial identifications of (anti)androgenic compounds in fish exposed to wastewater treatment works effluents. , 2010, Environmental science & technology.

[19]  Mutagenic potentials of Amberlite XAD-2-resin extracts obtained from river and drinking waters in the Northwest district of Chiba, Japan. , 2010, The Journal of toxicological sciences.

[20]  T. Ford,et al.  Semi-volatile organic compounds and trace elements in the Yangtze River source of drinking water , 2009, Ecotoxicology.

[21]  O. Fardel,et al.  Transcriptional signature of human macrophages exposed to the environmental contaminant benzo(a)pyrene. , 2010, Toxicological sciences : an official journal of the Society of Toxicology.

[22]  S. Jackson,et al.  Rosiglitazone produces a greater reduction in circulating platelet activity compared with gliclazide in patients with type 2 diabetes mellitus--an effect probably mediated by direct platelet PPARgamma activation. , 2008, Atherosclerosis.

[23]  T. Yu,et al.  Levels of organochlorine pesticides in natural water along the Yangtze River, from headstream to estuary, and factors determining these levels , 2011 .

[24]  M. Viant,et al.  Identifying health impacts of exposure to copper using transcriptomics and metabolomics in a fish model. , 2010, Environmental science & technology.

[25]  J. Lindon,et al.  'Metabonomics': understanding the metabolic responses of living systems to pathophysiological stimuli via multivariate statistical analysis of biological NMR spectroscopic data. , 1999, Xenobiotica; the fate of foreign compounds in biological systems.

[26]  M. Faisal,et al.  Interaction of cadmium and benzo[a]pyrene in mummichog (Fundulus heteroclitus): Effects on acute mortality , 1998 .

[27]  K. Kitchin,et al.  Dose response evaluation of gene expression profiles in the skin of K6/ODC mice exposed to sodium arsenite. , 2008, Toxicology and applied pharmacology.

[28]  N. Heaton,et al.  Identification of metabolites in human hepatic bile using 800 MHz 1H NMR spectroscopy, HPLC-NMR/MS and UPLC-MS. , 2009, Molecular bioSystems.

[29]  Takahiko Yoshida,et al.  Chronic health effects in people exposed to arsenic via the drinking water: dose-response relationships in review. , 2004, Toxicology and applied pharmacology.

[30]  John C. Lindon,et al.  NMR Spectroscopy of Biofluids , 1999 .

[31]  G. Sayler,et al.  Evaluation of polycyclic aromatic hydrocarbons in the activation of early growth response-1 and peroxisome proliferator activated receptors. , 2005, Toxicological sciences : an official journal of the Society of Toxicology.

[32]  Mark R Viant,et al.  International NMR-based environmental metabolomics intercomparison exercise. , 2009, Environmental science & technology.

[33]  T. Cullingford.  The ketogenic diet; fatty acids, fatty acid-activated receptors and neurological disorders. , 2004, Prostaglandins, leukotrienes, and essential fatty acids.

[34]  M. Leaver,et al.  A piscine glutathione S-transferase which efficiently conjugates the end-products of lipid peroxidation , 1998 .

[35]  M. Viant,et al.  Hepatic transcriptomic and metabolomic responses in the stickleback (Gasterosteus aculeatus) exposed to environmentally relevant concentrations of dibenzanthracene. , 2009, Environmental science & technology.

[36]  Jie Liu,et al.  Aberrant DNA methylation and gene expression in livers of newborn mice transplacentally exposed to a hepatocarcinogenic dose of inorganic arsenic. , 2007, Toxicology.

[37]  S. Schreiber,et al.  The association of fatty acid-binding protein 2 A54T polymorphism with postprandial lipemia depends on promoter variability. , 2007, Metabolism: clinical and experimental.

[38]  D. Zhao,et al.  Preliminary Risk Assessment of Trace Metal Pollution in Surface Water from Yangtze River in Nanjing Section, China , 2009, Bulletin of environmental contamination and toxicology.

[39]  Cécile Canlet,et al.  Identification of potential mechanisms of toxicity after di-(2-ethylhexyl)-phthalate (DEHP) adult exposure in the liver using a systems biology approach. , 2009, Toxicology and applied pharmacology.

[40]  T. Ebbels,et al.  NMR-based metabolic profiling identifies biomarkers of liver regeneration following partial hepatectomy in the rat. , 2010, Journal of proteome research.

[41]  D. Waxman,et al.  P450 gene induction by structurally diverse xenochemicals: central role of nuclear receptors CAR, PXR, and PPAR. , 1999, Archives of biochemistry and biophysics.

[42]  T. Sueyoshi,et al.  Nuclear Pregnane X Receptor Cross-talk with FoxA2 to Mediate Drug-induced Regulation of Lipid Metabolism in Fasting Mouse Liver* , 2007, Journal of Biological Chemistry.

[43]  V. Canzonieri,et al.  PPAR Signaling Pathway and Cancer-Related Proteins Are Involved in Celiac Disease-Associated Tissue Damage , 2010 .

[44]  Allan B. Okey,et al.  Role of Aryl Hydrocarbon Receptor-mediated Induction of the CYP1 Enzymes in Environmental Toxicity and Cancer* , 2004, Journal of Biological Chemistry.

[45]  F. Carvalho,et al.  Behaviour and biomarkers of oxidative stress in Gambusia holbrooki after acute exposure to widely used pharmaceuticals and a detergent. , 2008, Ecotoxicology and environmental safety.

[46]  Hong-Seog Park,et al.  Changes in gene expression profile of medaka with acute toxicity of Arochlor 1260, a polychlorinated biphenyl mixture. , 2010, Comparative biochemistry and physiology. Toxicology & pharmacology : CBP.

[47]  Huiru Tang,et al.  Systems biological responses to chronic perfluorododecanoic acid exposure by integrated metabonomic and transcriptomic studies. , 2009, Journal of proteome research.

[48]  D. Jewell,et al.  Drinking-Water Arsenic Exposure Modulates Gene Expression in Human Lymphocytes from a U.S. Population , 2008, Environmental health perspectives.

[49]  T. Shimada,et al.  Metabolic activation of polycyclic aromatic hydrocarbons to carcinogens by cytochromes P450 1A1 and1B1 , 2004, Cancer science.