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PMID: 18622026 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Ligand activation of peroxisome proliferator-activated receptor beta/delta (PPARbeta/delta) attenuates carbon tetrachloride hepatotoxicity by downregulating proinflammatory gene expression.

Toxicological sciences : an official journal of the Society of Toxicology ·Vol. 105 ·No. 2 ·2008-10-00 ·Pages 418-28

Shan W, Palkar PS, Murray IA, McDevitt EI, Kennett MJ, Kang BH, Isom HC, Perdew GH, Gonzalez FJ, Peters JM

Abstract

Peroxisome proliferator-activated receptor (PPAR) beta/delta-null mice exhibit exacerbated hepatotoxicity in response to administration of carbon tetrachloride (CCl(4)). To determine whether ligand activation of the receptor protects against chemical toxicity in the liver, wild-type and PPARbeta/delta-null mice were administered CCl(4) with or without coadministration of the highly specific PPARbeta/delta ligand GW0742. Biomarkers of liver toxicity, including serum alanine aminotransferase (ALT) and hepatic tumor necrosis factor (TNF) alpha mRNA, were significantly higher in CCl(4)-treated PPARbeta/delta-null mice compared to wild-type mice. Hepatic expression of TNF-like weak inducer of apoptosis receptor (TWEAKr) and S100 calcium-binding protein A6 (S100A6/calcyclin), genes involved in nuclear factor kappa B signaling, was higher in the CCl(4)-treated PPARbeta/delta-null mice compared to wild-type mice. GW0742 treatment resulted in reduced serum ALT concentration and lower expression of CCl(4)-induced TNF-alpha, S100A6, monocyte chemoattractant protein-1 (MCP1), and TWEAKr in wild-type mice, and these effects were not observed in PPARbeta/delta-null mice. Expression of TNF-alpha was higher in PPARbeta/delta-null primary hepatocytes in response to interleukin-1beta treatment compared to wild-type hepatocytes, but GW0742 did not significantly modulate TNF-alpha expression in hepatocytes from either genotype. While PPARbeta/delta-null hepatic stellate exhibited higher rates of proliferation compared to wild-type cells, GW0742 did not affect alpha-smooth muscle actin expression in these cells. Combined, these findings demonstrate that ligand activation of PPARbeta/delta protects against chemically induced hepatotoxicity by downregulating expression of proinflammatory genes. Hepatocytes and hepatic stellate cells do not appear to directly mediate the inhibitory effects of ligand activation of PPARbeta/delta in liver, suggesting the involvement of paracrine and autocrine events mediated by hepatic cells.

MeSH Terms
Animals Biomarkers/metabolism Carbon Tetrachloride Cell Proliferation/drug effects Cells, Cultured Chemical and Drug Induced Liver Injury Disease Models, Animal Dose-Response Relationship, Drug Down-Regulation Inflammation Mediators/metabolism Ligands Liver/drug effects,enzymology,pathology Liver Diseases/genetics,metabolism,prevention & control Male Mice Mice, Inbred C57BL Mice, Knockout PPAR delta/agonists,genetics,metabolism PPAR-beta/agonists,genetics,metabolism Protective Agents/pharmacology Thiazolidines/pharmacology Time Factors Tumor Necrosis Factor-alpha/genetics,metabolism
Chemicals
Biomarkers GW0072 Inflammation Mediators Ligands PPAR delta PPAR-beta Protective Agents Thiazolidines Tumor Necrosis Factor-alpha Carbon Tetrachloride
Authors & Affiliations
10 authors, click to expand affiliations / ORCID
Shan Weiwei
Department of Veterinary and Biomedical Sciences and The Center for Molecular Toxicology and Carcinogenesis, The Huck Institute of Life Sciences, The Pennsylvania State University, University Park, Pennsylvania 16802, USA.
Palkar Prajakta S
Murray Iain A
McDevitt Emily I
Kennett Mary J
Kang Boo Hyon
Isom Harriet C
Perdew Gary H
Gonzalez Frank J
Peters Jeffrey M
References (96)
96 references, click to expand
  1. Growth, adipose, brain, and skin alterations resulting from targeted disruption of the mouse peroxisome proliferator-activated receptor beta(delta).
    Mol Cell Biol. 2000 Jul;20(14):5119-28 PMID: 10866668
  2. The selective cyclooxygenase-2 inhibitor SC-236 reduces liver fibrosis by mechanisms involving non-parenchymal cell apoptosis and PPARgamma activation.
    FASEB J. 2005 Jul;19(9):1120-2 PMID: 15876570
  3. Isoform specific changes in PPAR alpha and beta in colon and breast cancer with differentiation.
    Biochem Biophys Res Commun. 2006 Feb 10;340(2):656-60 PMID: 16378595
  4. PPAR delta agonist L-165041 inhibits rat vascular smooth muscle cell proliferation and migration via inhibition of cell cycle.
    Atherosclerosis. 2009 Feb;202(2):446-54 PMID: 18585719
  5. Impaired skin wound healing in peroxisome proliferator-activated receptor (PPAR)alpha and PPARbeta mutant mice.
    J Cell Biol. 2001 Aug 20;154(4):799-814 PMID: 11514592
  6. PPARbeta-mediated growth suppression of baicalein and dexamethasone in human myeloma cells.
    Leukemia. 2007 Jan;21(1):187-90 PMID: 17082776
  7. TWEAK can induce pro-inflammatory cytokines and matrix metalloproteinase-9 in macrophages.
    Circ J. 2004 Apr;68(4):396-9 PMID: 15056843
  8. Activation of peroxisome proliferator-activated receptor (PPAR)delta promotes reversal of multiple metabolic abnormalities, reduces oxidative stress, and increases fatty acid oxidation in moderately obese men.
    Diabetes. 2008 Feb;57(2):332-9 PMID: 18024853
  9. Transforming growth factor-beta1 is a molecular target for the peroxisome proliferator-activated receptor delta.
    Circ Res. 2008 Feb 1;102(2):193-200 PMID: 18007025
  10. Deregulation of tumor angiogenesis and blockade of tumor growth in PPARbeta-deficient mice.
    EMBO J. 2007 Aug 8;26(15):3686-98 PMID: 17641685
  11. Rat PPARs: quantitative analysis in adult rat tissues and regulation in fasting and refeeding.
    Endocrinology. 2001 Oct;142(10):4195-202 PMID: 11564675
  12. Critical roles of PPAR beta/delta in keratinocyte response to inflammation.
    Genes Dev. 2001 Dec 15;15(24):3263-77 PMID: 11751632
  13. Crosstalk between peroxisome proliferator-activated receptor delta and VEGF stimulates cancer progression.
    Proc Natl Acad Sci U S A. 2006 Dec 12;103(50):19069-74 PMID: 17148604
  14. PPARdelta modulates lipopolysaccharide-induced TNFalpha inflammation signaling in cultured cardiomyocytes.
    J Mol Cell Cardiol. 2006 Jun;40(6):821-8 PMID: 16698033
  15. Mechanisms of hepatic fibrogenesis.
    Gastroenterology. 2008 May;134(6):1655-69 PMID: 18471545
  16. Ligand activation of peroxisome proliferator-activated receptor beta inhibits colon carcinogenesis.
    Cancer Res. 2006 Apr 15;66(8):4394-401 PMID: 16618765
  17. Prevention of ethanol-induced liver injury in rats by an agonist of peroxisome proliferator-activated receptor-gamma, pioglitazone.
    J Pharmacol Exp Ther. 2003 Sep;306(3):846-54 PMID: 12805475
  18. PPARbeta/delta ligands as modulators of the inflammatory response.
    Curr Opin Investig Drugs. 2008 May;9(5):463-9 PMID: 18465655
  19. Protective effects of a peroxisome proliferator-activated receptor-beta/delta agonist in experimental autoimmune encephalomyelitis.
    J Neuroimmunol. 2005 Nov;168(1-2):65-75 PMID: 16098614
  20. The peroxisome proliferator activated receptor δ is required for the differentiation of THP-1 monocytic cells by phorbol ester.
    Nucl Recept. 2003 Dec 11;1:9 PMID: 14670086
  21. The PPARdelta agonist GW0742X reduces atherosclerosis in LDLR(-/-) mice.
    Atherosclerosis. 2005 Jul;181(1):29-37 PMID: 15939051
  22. Peroxisome proliferator-activated receptor-beta/delta inhibits epidermal cell proliferation by down-regulation of kinase activity.
    J Biol Chem. 2005 Mar 11;280(10):9519-27 PMID: 15632134
  23. The Fn14 cytoplasmic tail binds tumour-necrosis-factor-receptor-associated factors 1, 2, 3 and 5 and mediates nuclear factor-kappaB activation.
    Biochem J. 2003 Apr 15;371(Pt 2):395-403 PMID: 12529173
  24. Peroxisome proliferator-activated receptor (PPAR)-beta/delta stimulates differentiation and lipid accumulation in keratinocytes.
    J Invest Dermatol. 2004 Apr;122(4):971-83 PMID: 15102088
  25. Smads 2 and 3 are differentially activated by transforming growth factor-beta (TGF-beta ) in quiescent and activated hepatic stellate cells. Constitutive nuclear localization of Smads in activated cells is TGF-beta-independent.
    J Biol Chem. 2003 Mar 28;278(13):11721-8 PMID: 12547835
  26. Tetradecylselenoacetic acid, a PPAR ligand with antioxidant, antiinflammatory, and hypolipidemic properties.
    Arterioscler Thromb Vasc Biol. 2007 Mar;27(3):628-34 PMID: 17185614
  27. A novel positive feedback loop between peroxisome proliferator-activated receptor-delta and prostaglandin E2 signaling pathways for human cholangiocarcinoma cell growth.
    J Biol Chem. 2006 Nov 10;281(45):33982-96 PMID: 16966336
  28. Peroxisome proliferator-activated receptor-beta signaling contributes to enhanced proliferation of hepatic stellate cells.
    Gastroenterology. 2003 Jan;124(1):184-201 PMID: 12512042
  29. Correlation between expression of peroxisome proliferator-activated receptor beta and squamous differentiation in epidermal and tracheobronchial epithelial cells.
    Mol Cell Endocrinol. 1999 Jan 25;147(1-2):85-92 PMID: 10195695
  30. Prostaglandin E(2) promotes colorectal adenoma growth via transactivation of the nuclear peroxisome proliferator-activated receptor delta.
    Cancer Cell. 2004 Sep;6(3):285-95 PMID: 15380519
  31. Peroxisome proliferator-activated receptor beta/delta activation improves angiotensin II-induced cardiac hypertrophy in vitro.
    Clin Exp Hypertens. 2008 Feb;30(2):109-19 PMID: 18293166
  32. Involvement of NF-kappaB in the regulation of S100A6 gene expression in human hepatoblastoma cell line HepG2.
    Biochem Biophys Res Commun. 2003 Jul 25;307(2):274-80 PMID: 12859951
  33. Inhibition of interleukin-1beta-induced group IIA secretory phospholipase A2 expression by peroxisome proliferator-activated receptors (PPARs) in rat vascular smooth muscle cells: cooperation between PPARbeta and the proto-oncogene BCL-6.
    Mol Cell Biol. 2007 Dec;27(23):8374-87 PMID: 17908795
  34. Peroxisome proliferator-activated receptor-beta/delta (PPARbeta/delta) ligands inhibit growth of UACC903 and MCF7 human cancer cell lines.
    Toxicology. 2008 Jan 14;243(1-2):236-43 PMID: 18054822
  35. ERK5 activation inhibits inflammatory responses via peroxisome proliferator-activated receptor delta (PPARdelta) stimulation.
    J Biol Chem. 2006 Oct 27;281(43):32164-74 PMID: 16943204
  36. PPARbeta/delta protects against experimental colitis through a ligand-independent mechanism.
    Dig Dis Sci. 2007 Nov;52(11):2912-9 PMID: 17404849
  37. Tumor necrosis factor-like weak inducer of apoptosis inhibits skeletal myogenesis through sustained activation of nuclear factor-kappaB and degradation of MyoD protein.
    J Biol Chem. 2006 Apr 14;281(15):10327-36 PMID: 16461349
  38. Role of prostacyclin versus peroxisome proliferator-activated receptor beta receptors in prostacyclin sensing by lung fibroblasts.
    Am J Respir Cell Mol Biol. 2006 Feb;34(2):242-6 PMID: 16239641
  39. PPARbeta agonists trigger neuronal differentiation in the human neuroblastoma cell line SH-SY5Y.
    J Cell Physiol. 2007 Jun;211(3):837-47 PMID: 17390299
  40. PPARalpha and PPARdelta activators inhibit cytokine-induced nuclear translocation of NF-kappaB and expression of VCAM-1 in EAhy926 endothelial cells.
    Eur J Pharmacol. 2002 Jan 25;435(2-3):143-51 PMID: 11821020
  41. PPARbeta/delta selectively induces differentiation and inhibits cell proliferation.
    Cell Death Differ. 2006 Jan;13(1):53-60 PMID: 16021179
  42. Tissue distribution and quantification of the expression of mRNAs of peroxisome proliferator-activated receptors and liver X receptor-alpha in humans: no alteration in adipose tissue of obese and NIDDM patients.
    Diabetes. 1997 Aug;46(8):1319-27 PMID: 9231657
  43. Fatty acids and eicosanoids regulate gene expression through direct interactions with peroxisome proliferator-activated receptors alpha and gamma.
    Proc Natl Acad Sci U S A. 1997 Apr 29;94(9):4318-23 PMID: 9113987
  44. Peroxisome proliferator-activated receptor beta (delta)-dependent regulation of ubiquitin C expression contributes to attenuation of skin carcinogenesis.
    J Biol Chem. 2004 May 28;279(22):23719-27 PMID: 15033975
  45. Differential expression of peroxisome proliferator-activated receptors (PPARs): tissue distribution of PPAR-alpha, -beta, and -gamma in the adult rat.
    Endocrinology. 1996 Jan;137(1):354-66 PMID: 8536636
  46. Adipocyte-derived Th2 cytokines and myeloid PPARdelta regulate macrophage polarization and insulin sensitivity.
    Cell Metab. 2008 Jun;7(6):485-95 PMID: 18522830
  47. The organization, promoter analysis, and expression of the human PPARgamma gene.
    J Biol Chem. 1997 Jul 25;272(30):18779-89 PMID: 9228052
  48. Prostacyclin-mediated activation of peroxisome proliferator-activated receptor delta in colorectal cancer.
    Proc Natl Acad Sci U S A. 2000 Nov 21;97(24):13275-80 PMID: 11087869
  49. PPARdelta-mediated antiinflammatory mechanisms inhibit angiotensin II-accelerated atherosclerosis.
    Proc Natl Acad Sci U S A. 2008 Mar 18;105(11):4277-82 PMID: 18337495
  50. Peroxisome proliferator-activated receptor beta/delta activation inhibits hypertrophy in neonatal rat cardiomyocytes.
    Cardiovasc Res. 2005 Mar 1;65(4):832-41 PMID: 15721863
  51. PPARdelta regulates glucose metabolism and insulin sensitivity.
    Proc Natl Acad Sci U S A. 2006 Feb 28;103(9):3444-9 PMID: 16492734
  52. Activation of peroxisome proliferator-activated receptor beta/delta inhibits lipopolysaccharide-induced cytokine production in adipocytes by lowering nuclear factor-kappaB activity via extracellular signal-related kinase 1/2.
    Diabetes. 2008 Aug;57(8):2149-57 PMID: 18443198
  53. Effects of di(2-ethylhexyl) phthalate, a widely used peroxisome proliferator and plasticizer, on cell growth in the human keratinocyte cell line NCTC 2544.
    J Toxicol Environ Health A. 2006 Mar;69(5):353-65 PMID: 16455614
  54. The toxicology of ligands for peroxisome proliferator-activated receptors (PPAR).
    Toxicol Sci. 2006 Apr;90(2):269-95 PMID: 16322072
  55. Increased infarct size and lack of hyperphagic response after focal cerebral ischemia in peroxisome proliferator-activated receptor beta-deficient mice.
    J Cereb Blood Flow Metab. 2006 Mar;26(3):433-45 PMID: 16094319
  56. Effects of bezafibrate, PPAR pan-agonist, and GW501516, PPARdelta agonist, on development of steatohepatitis in mice fed a methionine- and choline-deficient diet.
    Eur J Pharmacol. 2006 Apr 24;536(1-2):182-91 PMID: 16574099
  57. Deficiency of PPARbeta/delta in the epidermis results in defective cutaneous permeability barrier homeostasis and increased inflammation.
    J Invest Dermatol. 2008 Feb;128(2):370-7 PMID: 17713572
  58. Peroxisome proliferator-activated receptor expression and activation in normal human colonic epithelial cells and tubular adenomas.
    Scand J Gastroenterol. 2005 Feb;40(2):198-205 PMID: 15764152
  59. PPAR delta agonists stimulate oligodendrocyte differentiation in tissue culture.
    Glia. 2001 Mar 1;33(3):191-204 PMID: 11241737
  60. The mechanisms of action of PPARs.
    Annu Rev Med. 2002;53:409-35 PMID: 11818483
  61. Hypolipidemic drugs, polyunsaturated fatty acids, and eicosanoids are ligands for peroxisome proliferator-activated receptors alpha and delta.
    Proc Natl Acad Sci U S A. 1997 Apr 29;94(9):4312-7 PMID: 9113986
  62. Quantitative expression patterns of peroxisome proliferator-activated receptor-beta/delta (PPARbeta/delta) protein in mice.
    Biochem Biophys Res Commun. 2008 Jul 4;371(3):456-61 PMID: 18442472
  63. Peroxisome proliferator-activated receptor alpha negatively regulates the vascular inflammatory gene response by negative cross-talk with transcription factors NF-kappaB and AP-1.
    J Biol Chem. 1999 Nov 5;274(45):32048-54 PMID: 10542237
  64. Peroxisome proliferator-activated receptor delta as a molecular target to regulate lung cancer cell growth.
    FEBS Lett. 2005 Jul 4;579(17):3829-36 PMID: 15978581
  65. Peroxisome proliferator-activated receptor alpha, delta, gamma1 and gamma2 expressions are present in human monocyte-derived dendritic cells and modulate dendritic cell maturation by addition of subtype-specific ligands.
    Scand J Immunol. 2006 May;63(5):330-7 PMID: 16640656
  66. Activation of PPARdelta inhibits cardiac fibroblast proliferation and the transdifferentiation into myofibroblasts.
    Cardiovasc Res. 2007 Aug 1;75(3):519-29 PMID: 17543901
  67. Ligand activation of peroxisome proliferator-activated receptor-beta/delta (PPARbeta/delta) and inhibition of cyclooxygenase 2 (COX2) attenuate colon carcinogenesis through independent signaling mechanisms.
    Carcinogenesis. 2008 Jan;29(1):169-76 PMID: 17893232
  68. Liver fibrogenesis and the role of hepatic stellate cells: new insights and prospects for therapy.
    J Gastroenterol Hepatol. 1999 Jul;14(7):618-33 PMID: 10440206
  69. PPARdelta status and Apc-mediated tumourigenesis in the mouse intestine.
    Oncogene. 2004 Nov 25;23(55):8992-6 PMID: 15480419
  70. Activation of retinoic X receptor and peroxisome proliferator-activated receptor-gamma inhibits nitric oxide and tumor necrosis factor-alpha production in rat Kupffer cells.
    Hepatology. 2001 Jan;33(1):91-9 PMID: 11124825
  71. Gap junction-mediated intercellular communication in a long-term primary mouse hepatocyte culture system.
    Hepatology. 2003 Nov;38(5):1125-35 PMID: 14578851
  72. The PPARs: from orphan receptors to drug discovery.
    J Med Chem. 2000 Feb 24;43(4):527-50 PMID: 10691680
  73. Induction of differentiation in F9 cells and activation of peroxisome proliferator-activated receptor delta by valproic acid and its teratogenic derivatives.
    Mol Pharmacol. 2001 May;59(5):1269-76 PMID: 11306712
  74. Activation of PPARdelta alters lipid metabolism in db/db mice.
    FEBS Lett. 2000 May 19;473(3):333-6 PMID: 10818235
  75. Recent advances in peroxisome proliferator-activated receptor science.
    Curr Med Chem. 2003 Feb;10(4):267-80 PMID: 12570700
  76. Suppression of pro-inflammatory adhesion molecules by PPAR-delta in human vascular endothelial cells.
    Arterioscler Thromb Vasc Biol. 2008 Feb;28(2):315-21 PMID: 18048767
  77. A selective peroxisome proliferator-activated receptor delta agonist promotes reverse cholesterol transport.
    Proc Natl Acad Sci U S A. 2001 Apr 24;98(9):5306-11 PMID: 11309497
  78. PPARbeta/delta regulates paneth cell differentiation via controlling the hedgehog signaling pathway.
    Gastroenterology. 2006 Aug;131(2):538-53 PMID: 16890607
  79. PPARdelta regulates multiple proinflammatory pathways to suppress atherosclerosis.
    Proc Natl Acad Sci U S A. 2008 Mar 18;105(11):4271-6 PMID: 18337509
  80. RNA interference against peroxisome proliferator-activated receptor delta gene promotes proliferation of human colorectal cancer cells.
    Dis Colon Rectum. 2008 Mar;51(3):318-26; discussion 326-8 PMID: 18214615
  81. Tumor necrosis factor-like weak inducer of apoptosis increases the permeability of the neurovascular unit through nuclear factor-kappa B pathway activation.
    J Neurosci. 2005 Nov 2;25(44):10094-100 PMID: 16267216
  82. Cross-talk between peroxisome proliferator-activated receptor delta and cytosolic phospholipase A(2)alpha/cyclooxygenase-2/prostaglandin E(2) signaling pathways in human hepatocellular carcinoma cells.
    Cancer Res. 2006 Dec 15;66(24):11859-68 PMID: 17178883
  83. Interleukin-1 beta induction of TNF-alpha gene expression: involvement of protein kinase C.
    J Cell Physiol. 1992 Aug;152(2):264-73 PMID: 1639861
  84. Peroxisome proliferator-activated receptor-beta/delta (PPARbeta/delta) ligands do not potentiate growth of human cancer cell lines.
    Carcinogenesis. 2007 Dec;28(12):2641-9 PMID: 17693664
  85. Activation of peroxisome proliferator-activated receptor delta induces fatty acid beta-oxidation in skeletal muscle and attenuates metabolic syndrome.
    Proc Natl Acad Sci U S A. 2003 Dec 23;100(26):15924-9 PMID: 14676330
  86. Ligand activation of peroxisome proliferator-activated receptor-beta/delta(PPARbeta/delta) inhibits cell growth of human N/TERT-1 keratinocytes.
    Cell Signal. 2007 Jun;19(6):1163-71 PMID: 17254750
  87. Expression and localization of peroxisome proliferator-activated receptors and nuclear factor kappaB in normal and lesional psoriatic skin.
    J Invest Dermatol. 2003 Nov;121(5):1104-17 PMID: 14708613
  88. PPARgamma and PPARdelta negatively regulate specific subsets of lipopolysaccharide and IFN-gamma target genes in macrophages.
    Proc Natl Acad Sci U S A. 2003 May 27;100(11):6712-7 PMID: 12740443
  89. Modulation of keratinocyte gene expression and differentiation by PPAR-selective ligands and tetradecylthioacetic acid.
    J Invest Dermatol. 2001 May;116(5):702-12 PMID: 11348458
  90. Peroxisome proliferator-activated receptor-beta/delta protects against chemically induced liver toxicity in mice.
    Hepatology. 2008 Jan;47(1):225-35 PMID: 18038451
  91. Peroxisome proliferator-activated receptor-delta attenuates colon carcinogenesis.
    Nat Med. 2004 May;10(5):481-3 PMID: 15048110
  92. Alternative M2 activation of Kupffer cells by PPARdelta ameliorates obesity-induced insulin resistance.
    Cell Metab. 2008 Jun;7(6):496-507 PMID: 18522831
  93. Role of the Kupffer cell in mediating hepatic toxicity and carcinogenesis.
    Toxicol Sci. 2007 Mar;96(1):2-15 PMID: 17122412
  94. Differentiation of trophoblast giant cells and their metabolic functions are dependent on peroxisome proliferator-activated receptor beta/delta.
    Mol Cell Biol. 2006 Apr;26(8):3266-81 PMID: 16581799
  95. The PPARdelta agonist GW501516 suppresses interleukin-6-mediated hepatocyte acute phase reaction via STAT3 inhibition.
    Eur J Clin Invest. 2007 May;37(5):425-33 PMID: 17461989
  96. Activation of PPAR gamma and delta by conjugated linoleic acid mediates protection from experimental inflammatory bowel disease.
    Gastroenterology. 2004 Sep;127(3):777-91 PMID: 15362034
Article Info
Journal
Toxicological sciences : an official journal of the Society of Toxicology
Abbr.
Toxicol Sci
ISSN
1096-0929
DOI
10.1093/toxsci/kfn142
Published
2008-10-00
Epub
2008-00-12
Pages
418-28
Language
English
Region
United States
NLM ID
9805461
PMCID
PMC2527639
Subset
IM
Grants
NCI NIH HHS · CA023931 · United States
NCI NIH HHS · CA124533 · United States
NIEHS NIH HHS · ES04869 · United States
External Links
PubMed source DOI: 10.1093/toxsci/kfn142 PMC Full Text View journal details
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