Deoxynivalenol: Mechanisms of action, human exposure, and toxicological relevance

Archives of Toxicology

Volumn 84, Issue 9, 2010, Pages 663-679

  Pestka, James J ^a,b  

^a 234 GM Trout Building ^*  (United States)

^b MICHIGAN STATE UNIVERSITY   (United States)

Author keywords

Fungus; Fusarium; Gastroenteritis; Mycotoxin; Trichothecene

Indexed keywords

GROWTH HORMONE; VOMITOXIN;

ACUTE TOXICITY; ANOREXIA; CARCINOGENESIS; CELL DEATH; CELL DIFFERENTIATION; CELL PROLIFERATION; CEREAL; CHRONIC DISEASE; CYTOTOXICITY; DEVELOPMENTAL DISORDER; EXPOSURE; FOOD CONTAMINATION; FUNGAL PLANT DISEASE; FUSARIUM; GASTROENTERITIS; GENE EXPRESSION REGULATION; GENE INDUCTION; GROWTH RETARDATION; HUMAN; IMMUNOTOXICITY; INFLAMMATION; INNATE IMMUNITY; INTOXICATION; MACROMOLECULE; MATERNAL DISEASE; NEUROENDOCRINE DISEASE; NONHUMAN; PATHOPHYSIOLOGY; PRIORITY JOURNAL; REPRODUCTIVE TOXICITY; REVIEW; RIBOTOXIC STRESS; RISK ASSESSMENT; RISK MANAGEMENT; SIGNAL TRANSDUCTION; TERATOGENICITY; TOXICOKINETICS; TOXIN ANALYSIS; TOXIN SYNTHESIS; TRANSLATION REGULATION; VOMITING;

ANIMALS; CEREALS; DISEASE MODELS, ANIMAL; ENVIRONMENTAL EXPOSURE; FOOD MICROBIOLOGY; FUSARIUM; GASTROENTERITIS; GASTROINTESTINAL TRACT; HUMANS; MALE; MICE; RIBOSOMES; RISK ASSESSMENT; SIGNAL TRANSDUCTION; SWINE; TRANSLATIONAL RESEARCH; TRICHOTHECENES;

ANIMALIA; FUNGI; FUSARIUM; HORDEUM; SUIDAE; TRITICUM AESTIVUM; ZEA MAYS;

EID: 77957802278     PISSN: 03405761     EISSN: None     Source Type: Journal    
DOI: 10.1007/s00204-010-0579-8     Document Type: Review

References (166)

1. HK Abbas CJ Mirocha J Tuite 1986 Natural occurrence of deoxynivalenol, 15-acetyl-deoxynivalenol, and zearalenone in refusal factor corn stored since 1972 Appl Environ Microbiol 51 841 843 1:CAS:528:DyaL28Xltlags74%3D 2939798
2. F Accensi P Pinton P Callu N Abella-Bourges JF Guelfi F Grosjean IP Oswald 2006 Ingestion of low doses of deoxynivalenol does not affect hematological, biochemical, or immune responses of piglets J Anim Sci 84 1935 1942 1:CAS:528:DC%2BD28Xmt1aqtLg%3D 16775078
3. CJ Amuzie JJ Pestka 2010 Suppression of insulin-like growth factor acid-labile subunit expression-a novel mechanism for deoxynivalenol-induced growth retardation Toxicol Sci 113 412 421 1:CAS:528:DC%2BC3cXntlGmtg%3D%3D 19805407
4. CJ Amuzie J Shinozuka JJ Pestka 2009 Induction of suppressors of cytokine signaling by the trichothecene deoxynivalenol in the mouse Toxicol Sci 111 277 287 1:CAS:528:DC%2BD1MXhtFaku7nK 19625342
5. DL Arnold PF McGuire EA Nera KF Karpinski MG Bickis ZZ Zawidzka S Fernie RF Vesonder 1986 The toxicity of orally administered deoxynivalenol (vomitoxin) in rats and mice Food Chem Toxicol 24 935 941 1:CAS:528:DyaL2sXmsF2rsw%3D%3D 3781440
6. OJ Azcona Y Ouyang J Murtha FS Chu JJ Pestka 1995 Induction of cytokine mRNAs in mice after oral exposure to the trichothecene vomitoxin (deoxynivalenol): relationship to toxin distribution and protein synthesis inhibition Toxicol Appl Pharmacol 133 109 120
7. HK Bae JJ Pestka 2008 Deoxynivalenol induces p38 interaction with the ribosome in monocytes and macrophages Toxicol Sci 105 59 66 1:CAS:528: DC%2BD1cXps12itb4%3D 18502741
8. HK Bae JS Gray M Li L Vines J Kim JJ Pestka 2010 Hematopoietic cell kinase associates with the 40S ribosomal subunit and mediates the ribotoxic stress response to deoxynivalenol in mononuclear phagocytes Toxicol Sci 115 444 452 1:CAS:528:DC%2BC3cXmsVGmsLY%3D 20181660
9. F Bensassi E El Golli-Bennour S Abid-Essefi C Bouaziz MR Hajlaoui H Bacha 2009 Pathway of deoxynivalenol-induced apoptosis in human colon carcinoma cells Toxicology 264 104 109 1:CAS:528:DC%2BD1MXhtV2lt7%2FE 19664677
10. B Bergsjo T Matre I Nafstad 1992 Effects of diets with graded levels of deoxynivalenol on performance in growing pigs Zentralbl Veterinarmed[A] 39 752 758 1:STN:280:DyaK3s7ltVOgsg%3D%3D
11. B Bergsjo W Langseth I Nafstad JH Jansen HJ Larsen 1993 The effects of naturally deoxynivalenol-contaminated oats on the clinical condition, blood parameters, performance and carcass composition of growing pigs Vet Res Commun 17 283 294 1:STN:280:DyaK2c7ps1Kqtg%3D%3D 8146954
12. F Berthiller C Dall'Asta R Schuhmacher M Lemmens G Adam R Krska 2005 Masked mycotoxins: determination of a deoxynivalenol glucoside in artificially and naturally contaminated wheat by liquid chromatography-tandem mass spectrometry J Agric Food Chem 53 3421 3425 1:CAS:528:DC%2BD2MXivFGksLg%3D 15853382
13. RV Bhat SR Beedu Y Ramakrishna KL Munshi 1989 Outbreak of trichothecene mycotoxicosis associated with consumption of mould-damaged wheat production in Kashmir Valley, India Lancet 333 35 37
14. HL Borison 1989 Area postrema: chemoreceptor circumventricular organ of the medulla oblongata Prog Neurobiol 32 351 390 1:STN:280:DyaL1M3otlWlsw%3D%3D 2660187
15. Canady RA, Coker RD, Rgan SK, Krska R, Kuiper-Goodman T, Olsen M, Pestka JJ, Resnik S, Schlatter J (2001) Deoxynivalenol. Safety evaluation of certain mycotoxins in food. Fifty-sixth report of the Joint FAO/WHO Expert Committee on Food Additives. WHO Food Additives Series 47. International Programme on Chemical Safety-World Health Organization-Geneva, pp 420-555
16. MA Castillo R Montes A Navarro R Segarra G Cuesta E Hernandez 2008 Occurrence of deoxynivalenol and nivalenol in Spanish corn-based food products J Food Compos Anal 21 423 427 1:CAS:528:DC%2BD1cXntlSnurw%3D
17. V Cecarini J Gee E Fioretti M Amici M Angeletti AM Eleuteri JN Keller 2007 Protein oxidation and cellular homeostasis: emphasis on metabolism Biochim Biophys Acta 1773 93 104 1:CAS:528:DC%2BD2sXhtVChtb0%3D 17023064
18. RP Cherla SY Lee PL Mees VL Tesh 2006 Shiga toxin 1-induced cytokine production is mediated by MAP kinase pathways and translation initiation factor eIF4E in the macrophage-like THP-1 cell line J Leukoc Biol 79 397 407 1:CAS:528:DC%2BD28Xht12rur8%3D 16301326
19. HJ Choi H Yang SH Park Y Moon 2009 HuR/ELAVL1 RNA binding protein modulates interleukin-8 induction by muco-active ribotoxin deoxynivalenol Toxicol Appl Pharmacol 240 46 54 1:CAS:528:DC%2BD1MXhtV2rtrfM 19591856
20. YJ Chung HR Zhou JJ Pestka 2003 Transcriptional and posttranscriptional roles for p38 mitogen-activated protein kinase in upregulation of TNF-alpha expression by deoxynivalenol (vomitoxin) Toxicol Appl Pharmacol 193 188 201 1:CAS:528:DC%2BD3sXpsVSmu7c%3D 14644621
21. DE Clark PJ Wellman RB Harvey MS Lerma 1987 Effects of vomitoxin (deoxynivalenol) on conditioned saccharin aversion and food consumption in adult rats Pharmacol Biochem Behav 27 247 252 1:CAS:528:DyaL2sXltFSktb4%3D 3628439
22. TFX Collins RL Sprando TN Black N Olejnik RM Eppley FA Hines J Rorie DI Ruggles 2006 Effects of deoxynivalenol (DON, vomitoxin) on in utero development in rats Food Chem Toxicol 44 747 757 1:CAS:528:DC%2BD28Xjs1aitbw%3D 16325976
23. BA Croker H Kiu SE Nicholson 2008 SOCS regulation of the JAK/STAT signalling pathway Semin Cell Dev Biol 19 414 422 1:CAS:528:DC%2BD1cXhtFOrurrM 18708154
24. C Debouck E Haubruge P Bollaerts D van Bignoot Y Brostaux A Werry M Rooze 2001 Skeletal deformities induced by the intraperitoneal administration of deoxynivalenol (vomitoxin) in mice Int Orthop 25 194 198 1:STN:280: DC%2BD38%2FisFCltw%3D%3D 11482540
25. SD Der YL Yang C Weissmann BR Williams 1997 A double-stranded RNA-activated protein kinase-dependent pathway mediating stress-induced apoptosis Proc Natl Acad Sci USA 94 3279 3283 1:CAS:528:DyaK2sXisVKgu78%3D 9096384
26. BK English JN Ihle A Myracle T Yi 1993 Hck tyrosine kinase activity modulates tumor necrosis factor production by murine macrophages J Exp Med 178 1017 1022 1:CAS:528:DyaK3sXlsFOqu7Y%3D 8350043
27. BK English SL Orlicek Z Mei EA Meals 1997 Bacterial LPS and IFN-gamma trigger the tyrosine phosphorylation of vav in macrophages: evidence for involvement of the hck tyrosine kinase J Leukoc Biol 62 859 864 1:CAS:528:DyaK2sXnvFSqt7w%3D 9400828
28. Eriksen GS, Alexander J (1998) Fusarium toxins in cereals-a risk assessment. Nordic Council of Ministers, Copenhagen
29. M Ernst M Inglese GM Scholz KW Harder FJ Clay S Bozinovski P Waring R Darwiche T Kay P Sly R Collins D Turner ML Hibbs GP Anderson AR Dunn 2002 Constitutive activation of the SRC family kinase Hck results in spontaneous pulmonary inflammation and an enhanced innate immune response J Exp Med 196 589 604 1:CAS:528:DC%2BD38XmvFKqtLo%3D 12208875
30. J Fioramonti C Dupuy J Dupuy L Bueno 1993 The mycotoxin, deoxynivalenol, delays gastric emptying through serotonin-3 receptors in rodents J Pharmacol Exp Ther 266 1255 1260 1:CAS:528:DyaK3sXmsVegsbc%3D 8371135
31. JH Forsell MF Witt JH Tai R Jensen JJ Pestka 1986 Effects of 8-week exposure of the B6C3F1 mouse to dietary deoxynivalenol (vomitoxin) and zearalenone Food Chem Toxicol 24 213 219 1:CAS:528:DyaL28XktVGhu7k%3D 2937701
32. JH Forsell R Jensen JH Tai M Witt WS Lin JJ Pestka 1987 Comparison of acute toxicities of deoxynivalenol (vomitoxin) and 15-acetyldeoxynivalenol in the B6C3F1 mouse Food Chem Toxicol 25 155 162 1:CAS:528:DyaL2sXktVagsbw%3D 3557238
33. DM Forsyth T Yoshizawa N Morooka J Tuite 1977 Emetic and refusal activity of deoxynivalenol to swine Appl Environ Microbiol 34 547 552 1:CAS:528:DyaE1cXosVeitQ%3D%3D 931376
34. DW Friend HL Trenholm JI Elliot BK Thompson KE Hartin 1982 Effect of feeding vomitoxin-contaminated wheat to pigs CanJ Anim Sci 62 1211 1222 1:CAS:528:DyaL3sXhsF2hsb0%3D
35. R Froquet Y Sibiril D Parent-Massin 2001 Trichothecene toxicity on human megakaryocyte progenitors (CFU-MK) Human Exper Toxicol 20 84 89 1:CAS:528:DC%2BD3MXmvFOitrY%3D
36. KC Goh MJ deVeer BR Williamss 2000 The protein kinase PKR is required for p38 MAPK activation and the innate immune response to bacterial endotoxin EMBO J 19 4292 4297 1:CAS:528:DC%2BD3cXnt1yrtr8%3D 10944112
37. JS Gray JJ Pestka 2007 Transcriptional regulation of deoxynivalenol- induced IL-8 expression in human monocytes Toxicol Sci 99 502 511 1:CAS:528:DC%2BD2sXhtFKru7zI 17636245
38. JS Gray HK Bae JC Li AS Lau JJ Pestka 2008 Double-stranded RNA-activated protein kinase mediates induction of interleukin-8 expression by deoxynivalenol, Shiga toxin 1, and ricin in monocytes Toxicol Sci 105 322 330 1:CAS:528:DC%2BD1cXhtFWit7fN 18599499
39. JD Groopman TW Kensler 2005 Role of metabolism and viruses in aflatoxin-induced liver cancer Toxicol Appl Pharmacol 206 131 137 1:CAS:528:DC%2BD2MXlsVCiu7w%3D 15967201
40. JF Grove 1988 Non-macrocyclic trichothecenes Nat Prod Rep 5 187 209 1:CAS:528:DyaL1MXktl2muro%3D 3062504
41. JF Grove 1993 Macrocyclic trichothecenes Nat Prod Rep 10 429 448 1:CAS:528:DyaK2cXlsVOjsA%3D%3D
42. JF Grove 2000 Non-macrocyclic trichothecenes. Part 2 Prog Chem Org Nat Prod 69 1 70
43. He K, Pestka JJ (2010) Deoxynivalenol-induced modulation of microRNA expression in RAW 264.7 macrophages-A potential novel mechanism for translational inhibition. The Toxicologist (Toxicol Sci) 114(Suppl):310
44. RP Hopton E Turner VJ Burley PC Turner J Fisher 2010 Urine metabolite analysis as a function of deoxynivalenol exposure: an NMR-based metabolomics investigation Food Addit Contam Part A Chem Anal Control Expo Risk Assess 27 255 261 1:CAS:528:DC%2BD1MXhsFensbzK 20013448
45. DM Hughes MJ Gahl CH Graham SL Grieb 1999 Overt signs of toxicity to dogs and cats of dietary deoxynivalenol J Anim Sci 77 693 700 1:CAS:528: DyaK1MXjs1ers7w%3D 10229366
46. G Hunder K Schumann G Strugala J Gropp B Fichtl W Forth 1991 Influence of subchronic exposure to low dietary deoxynivalenol, a trichothecene mycotoxin, on intestinal absorption of nutrients in mice Food Chem Toxicol 29 809 814 1:CAS:528:DyaK38XnvVahtw%3D%3D 1765325
47. JN Hunt 1980 A possible relation between the regulation of gastric emptying and food intake Am J Physiol 239 G1 G4 1:STN:280:DyaL3c3jvFKqtg%3D%3D 7395999
48. Z Islam JJ Pestka 2003 Role of IL-1 beta in endotoxin potentiation of deoxynivalenol-induced corticosterone response and leukocyte apoptosis in mice Toxicol Sci 74 93 102 1:CAS:528:DC%2BD3sXkvVSmtbk%3D 12773775
49. Z Islam JJ Pestka 2006 LPS priming potentiates and prolongs proinflammatory cytokine response to the trichothecene deoxynivalenol in the mouse Toxicol Appl Pharmacol 211 53 63 1:CAS:528:DC%2BD28XhtFWjtL8%3D 16009389
50. Z Islam M Nagase A Ota S Ueda T Yoshizawa N Sakato 1998 Structure-function relationship of T-2 toxin and its metabolites in inducing thymic apoptosis in vivo in mice Biosci Biotechnol Biochem 62 1492 1497 1:CAS:528:DyaK1cXlvFemsrg%3D 9757554
51. Z Islam M Nagase T Yoshizawa KE Yamauchi N Sakato 1998 T-2 toxin induces thymic apoptosis in vivo in mice Toxicol Appl Pharmacol 148 205 214 1:CAS:528:DyaK1cXht12itLk%3D 9473527
52. Z Islam YS Moon HR Zhou LE King PJ Fraker JJ Pestka 2002 Endotoxin potentiation of trichothecene-induced lymphocyte apoptosis is mediated by up-regulation of glucocorticoids Toxicol Appl Pharmacol 180 43 55 1:CAS:528:DC%2BD38XitlOrtrY%3D 11922776
53. Z Islam LE King PJ Fraker JJ Pestka 2003 Differential induction of glucocorticoid-dependent apoptosis in murine lymphoid subpopulations in vivo following coexposure to lipopolysaccharide and vomitoxin (deoxynivalenol) Toxicol Appl Pharmacol 187 69 79 1:CAS:528:DC%2BD3sXitVKmsb0%3D 12649039
54. Z Islam JS Gray JJ Pestka 2006 p38 Mitogen-activated protein kinase mediates IL-8 induction by the ribotoxin deoxynivalenol in human monocytes Toxicol Appl Pharmacol 213 235 244 1:CAS:528:DC%2BD28Xltl2htrk%3D 16364386
55. F Iverson C Armstrong E Nera J Truelove S Fernie P Scott R Stapley S Hayward S Gunner 1995 Chronic feeding study of deoxynivalenol in B6C3F1 male and female mice Teratog Carcinog Mutagen 15 283 306 1:CAS:528:DyaK28XislyhtL4%3D 8732880
56. Q Jia HR Zhou M Bennink JJ Pestka 2004 Docosahexaenoic acid attenuates mycotoxin-induced immunoglobulin a nephropathy, interleukin-6 transcription, and mitogen-activated protein kinase phosphorylation in mice J Nutr 134 3343 3349 1:CAS:528:DC%2BD2cXhtVyitbbI 15570035
57. Q Jia HR Zhou Y Shi JJ Pestka 2006 Docosahexaenoic acid consumption inhibits deoxynivalenol-induced CREB/ATF1 activation and IL-6 gene transcription in mouse macrophages J Nutr 136 366 372 1:CAS:528:DC%2BD28Xht1Wis7Y%3D 16424113
58. Joffe AZ (1978) Fusarium poae and F. sporotichiodes as principal causal agents of alimentary toxic aleukia. In: Wyllie TD, Morehouse LG (eds) Mycotoxic fungi, mycotoxins, mycotoxicoses: an encylcopedic handbook. Dekker, New York, pp 21-86
59. KS Khera C Whalen G Angers T Kuiper Goodman 1982 The embryotoxicity of vomitoxin in mice Teratology 25 A54 A54
60. KS Khera C Whalen G Angers RF Vesonder T Kuiper-Goodman 1982 Embryotoxicity of 4-deoxynivalenol (vomitoxin) in mice Bull Environ Contam Toxicol 29 487 491 1:CAS:528:DyaL3sXjs1Cq 7171859
61. KS Khera DL Arnold C Whalen G Angers PM Scott 1984 Vomitoxin (4-deoxynivalenol): effects on reproduction of mice and rats Toxicol Appl Pharmacol 74 345 356 1:CAS:528:DyaL2cXltVGnurY%3D 6740683
62. KS Khera C Whalen G Angers 1986 A teratology study on vomitoxin (4-deoxynivalenol) in rabbits Food Chem Toxicol 24 421 424 1:CAS:528: DyaL28XmtVCmsro%3D 3744196
63. MM Kincaid AA Cooper 2007 Misfolded proteins traffic from the endoplasmic reticulum (ER) due to ER export signals Mol Biol Cell 18 455 463 1:CAS:528:DC%2BD2sXhsFarsLc%3D 17108324
64. S Kinser Q Jia M Li A Laughter P Cornwell JC Corton J Pestka 2004 Gene expression profiling in spleens of deoxynivalenol-exposed mice: immediate early genes as primary targets J Toxicol Environ Health A 67 1423 1441 1:CAS:528:DC%2BD2cXntlOkurk%3D 15371230
65. S Kinser M Li Q Jia JJ Pestka 2005 Truncated deoxynivalenol-induced splenic immediate early gene response in mice consuming (n-3) polyunsaturated fatty acids J Nutr Biochem 16 88 95 1:CAS:528:DC%2BD2MXoslCntw%3D%3D 15681167
66. M Kolf-Clauw J Castellote B Joly N Bourges-Abella I Raymond-Letron P Pinton IP Oswald 2009 Development of a pig jejunal explant culture for studying the gastrointestinal toxicity of the mycotoxin deoxynivalenol: histopathological analysis Toxicol In Vitro 23 1580 1584 1:CAS:528:DC%2BD1MXhsVajtb%2FP 19607908
67. V Korcheva J Wong M Lindauer DB Jacoby MS Iordanov B Magun 2007 Role of apoptotic signaling pathways in regulation of inflammatory responses to ricin in primary murine macrophages Mol Immunol 44 2761 2771 1:CAS:528: DC%2BD2sXhvVSlsbc%3D 17257680
68. Krantis AC, Durst T (2006) Novel multi-ring organic compounds for regulating gut motility, food intake and weight gain. World Intellectual Property Organization. WO/2006/006082. http://www.wipo.int/pctdb/en/wo.jsp?WO= 2006006082
69. Kuiper-Goodman T (1994) Prevention of mycotoxicoses through risk management and risk assessment. In: Miller JD, Trenholm HL (eds) Mycotoxins in grain. Eagan Press, St.Paul, pp 439-469
70. JC Larsen J Hunt I Perrin P Ruckenbauer 2004 Workshop on trichothecenes with a focus on DON: summary report Toxicol Lett 153 1 22 1:CAS:528: DC%2BD2cXntlGlt78%3D 15342076
71. S Lautraite D ParentMassin B Rio H Hoellinger 1997 In vitro toxicity induced by deoxynivalenol (DON) on human and rat granulomonocytic progenitors Cell Biol Toxicol 13 175 183 1:CAS:528:DyaK2sXisleitLk%3D 9088627
72. G Le Drean M Auffret P Batina F Arnold Y Sibiril D Arzur D Parent-Massin 2005 Myelotoxicity of trichothecenes and apoptosis: an in vitro study on human cord blood CD34(+) hematopoietic progenitor Toxicol In Vitro 19 1015 1024 1:CAS:528:DC%2BD2MXht1SksL%2FI 15908172
73. JC Leblanc A Tard JL Volatier P Verger 2005 Estimated dietary exposure to principal food mycotoxins from the first French Total Diet Study Food Addit Contam 22 652 672 1:CAS:528:DC%2BD2MXmt1CjsLs%3D 16019841 (Pubitemid 41001289)
74. Leyva-Illades D, Cherla RP, Galindo CL, Chopra AK, Tesh VL (2010) Global transcriptional response of macrophage-like THP-1 cells to Shiga toxin type 1. Infect Immun (in press)
75. Y Li 2007 Sensory signal transduction in the vagal primary afferent neurons Curr Med Chem 14 2554 2563 1:CAS:528:DC%2BD2sXhtFGmsrrN 17979708
76. MX Li JJ Pestka 2008 Comparative induction of 28S ribosomal RNA cleavage by ricin and the trichothecenes deoxynivalenol and T-2 toxin in the macrophage Toxicol Sci 105 67 78 1:CAS:528:DC%2BD1cXps12itLc%3D 18535001
77. SG Li YL Ouyang WM Dong JJ Pestka 1997 Superinduction of IL-2 gene expression by vomitoxin (deoxynivalenol) involves increased mRNA stability Toxicol Appl Pharmacol 147 331 342 1:CAS:528:DyaK1cXjt1Kkug%3D%3D 9439728
78. S Li Y Ouyang GH Yang JJ Pestka 2000 Modulation of transcription factor AP-1 activity in murine EL-4 thymoma cells by vomitoxin (deoxynivalenol) Toxicol Appl Pharmacol 163 17 25 1:CAS:528:DC%2BD3cXovVaksw%3D%3D 10662601
79. Luo X (1994) Food poisoning caused by Fusarium toxins. Proceedings of the Second Asian Conference on Food Safety. ILSI Thailand, pp 129-136
80. M Maresca R Mahfoud N Garmy J Fantini 2002 The mycotoxin deoxynivalenol affects nutrient absorption in human intestinal epithelial cells J Nutr 132 2723 2731 1:CAS:528:DC%2BD38XntFOgsb8%3D 12221236
81. M Maresca N Yahi L Younes-Sakr M Boyron B Caporiccio J Fantini 2008 Both direct and indirect effects account for the pro-inflammatory activity of enteropathogenic mycotoxins on the human intestinal epithelium: stimulation of interleukin-8 secretion, potentiation of interleukin-1 beta effect and increase in the transepithelial passage of commensal bacteria Toxicol Appl Pharmacol 228 84 92 1:CAS:528:DC%2BD1cXjs1Sktrw%3D 18308354
82. JE McLaughlin MA Bin-Umer A Tortora N Mendez S McCormick NE Tumer 2009 A genome-wide screen in Saccharomyces cerevisiae reveals a critical role for the mitochondria in the toxicity of a trichothecene mycotoxin Proc Natl Acad Sci USA 106 21883 21888 1:CAS:528:DC%2BC3cXltVKruw%3D%3D 20007368
83. M McMullen R Jones D Gallenberg 1997 Scab of wheat and barley: a re-emerging disease of devasting impact Plant Dis 81 1340 1348
84. FA Meky PC Turner AE Ashcroft JD Miller YL Qiao MJ Roth CP Wild 2003 Development of a urinary biomarker of human exposure to deoxynivalenol Food Chem Toxicol 41 265 273 1:CAS:528:DC%2BD38XptlCksb8%3D 12480302
85. K Miura Y Nakajima N Yamanaka K Terao T Shibato S Ishino 1998 Induction of apoptosis with fusarenon-X in mouse thymocytes Toxicology 127 195 206 1:CAS:528:DyaK1cXks1Omt7o%3D 9699806
86. Y Moon JJ Pestka 2002 Vomitoxin-induced cyclooxygenase-2 gene expression in macrophages mediated by activation of ERK and p38 but not JNK mitogen-activated protein kinases Toxicol Sci 69 373 382 1:CAS:528: DC%2BD38XnvVelt70%3D 12377986
87. Y Moon JJ Pestka 2003 Cyclooxygenase-2 mediates interleukin-6 upregulation by vomitoxin (deoxynivalenol) in vitro and in vivo Toxicol Appl Pharmacol 187 80 88 1:CAS:528:DC%2BD3sXitVKmsbo%3D 12649040
88. Y Moon R Uzarski JJ Pestka 2003 Relationship of trichothecene structure to COX-2 induction in the macrophage: selective action of type B (8-keto) trichothecenes J Toxicol Environ Health A 66 1967 1983 1:CAS:528: DC%2BD3sXns1GqsbY%3D 14514436
89. RE Morrissey 1984 Teratological study of Fischer rats fed diet containing added vomitoxin Food Chem Toxicol 22 453 457 1:CAS:528:DyaL2cXlt1CmsL4%3D 6539735
90. RE Morrissey RF Vesonder 1985 Effect of deoxynivalenol (vomitoxin) on fertility, pregnancy, and postnatal development of Sprague-Dawley rats Appl Environ Microbiol 49 1062 1066 1:CAS:528:DyaL2MXktFyis78%3D 4004229
91. RE Morrissey WP Norred RF Vesonder 1985 Subchronic toxicity of vomitoxin in Sprague-Dawley rats Food Chem Toxicol 23 995 999 1:CAS:528:DyaL28XhtVCjsrw%3D 2934304
92. M Nagase MM Alam A Tsushima T Yoshizawa N Sakato 2001 Apoptosis induction by T-2 toxin: activation of caspase-9, caspase-3, and DFF-40/CAD through cytosolic release of cytochrome c in HL-60 cells Biosci Biotechnol Biochem 65 1741 1747 1:CAS:528:DC%2BD3MXmslSltL0%3D 11577712
93. P Nejdfors M Ekelund B Jeppsson BR Westrom 2000 Mucosal in vitro permeability in the intestinal tract of the pig, the rat, and man: spe Scand J Gastroenterol 35 501 507 1:CAS:528:DC%2BD3cXktlWrtLg%3D 10868453
94. C Nielsen H Lippke A Didier R Dietrich E Martlbauer 2009 Potential of deoxynivalenol to induce transcription factors in human hepatoma cells Mol Nutr Food Res 53 479 491 1:CAS:528:DC%2BD1MXlsVWgsro%3D 19360757
95. HE Ok HJ Kim TY Cho KS Oh HS Chun 2009 Determination of deoxynivalenol in cereal-based foods and estimation of dietary exposure J Toxicol Environ Health Part A Current Issues 72 1424 1430 1:CAS:528:DC%2BD1MXhsValsLnN
96. KP Ossenkopp M Hirst WA Rapley 1994 Deoxynivalenol (vomitoxin)-induced conditioned taste aversions in rats are mediated by the chemosensitive area postrema Pharmacol Biochem Behav 47 363 367 1:CAS:528:DyaK2cXpvV2qsQ%3D%3D 8146230
97. YL Ouyang S Li JJ Pestka 1996 Effects of vomitoxin (deoxynivalenol) on transcription factor NF-kappa B/Rel binding activity in murine EL-4 thymoma and primary CD4 + T cells Toxicol Appl Pharmacol 140 328 336 1:CAS:528: DyaK28Xmt12jurw%3D 8887449
98. Paterson RRM, Lima N (2009) How will climate change affect mycotoxins in food? Food Res Int (in press)
99. JJ Pestka 2007 Deoxynivalenol: Toxicity, mechanisms and animal health risks Anim Feed Sci Technol 137 283 298 1:CAS:528:DC%2BD2sXpt1Kls70%3D
100. Pestka JJ (2008) Mechanisms of deoxynivalenol-induced gene expression and apoptosis. Food Addit Contam (in press)
101. JJ Pestka CJ Amuzie 2008 Tissue distribution and proinflammatory cytokine gene expression following acute oral exposure to deoxynivalenol: comparison of weanling and adult mice Food Chem Toxicol 46 2826 2831 1:CAS:528: DC%2BD1cXoslCntro%3D 18614267
102. JJ Pestka AT Smolinski 2005 Deoxynivalenol: toxicology and potential effects on humans J Toxicol Environ Health B Crit Rev 8 39 69 1:CAS:528:DC%2BD2MXns1ynsA%3D%3D 15762554
103. JJ Pestka WS Lin ER Miller 1987 Emetic activity of the trichothecene 15-acetyldeoxynivalenol in swine Food Chem Toxicol 25 855 858 1:CAS:528:DyaL1cXntVCjuw%3D%3D 3692388
104. JJ Pestka D Yan LE King 1994 Flow cytometric analysis of the effects of in vitro exposure to vomitoxin (deoxynivalenol) on apoptosis in murine T-cells, B-cells and IgA(+)-cells Food Chem Toxicol 32 1125 1136 1:CAS:528: DyaK2MXjtFyqtrs%3D 7813984
105. JJ Pestka HR Zhou Y Moon YJ Chung 2004 Cellular and molecular mechanisms for immune modulation by deoxynivalenol and other trichothecenes: unraveling a paradox Toxicol Lett 153 61 73 1:CAS:528:DC%2BD2cXntlGlt7k%3D 15342082
106. JJ Pestka RL Uzarski Z Islam 2005 Induction of apoptosis and cytokine production in the Jurkat human T cells by deoxynivalenol: role of mitogen-activated protein kinases and comparison to other 8-ketotrichothecenes Toxicology 206 207 219 1:CAS:528:DC%2BD2cXhtVKlu7bM 15588914
107. Pieters MN, Fiolet DCM, Baars AJ (1998) Deoxynivalenol: derivation of concentration limits in wheat and wheat containing food products. National Institute of Public Health and the Environment, Bilthoven, pp 1-32
108. P Pinton JP Nougayrede JC Del Rio C Moreno DE Marin L Ferrier AP Bracarense M Kolf-Clauw IP Oswald 2009 The food contaminant deoxynivalenol, decreases intestinal barrier permeability and reduces claudin expression Toxicol Appl Pharmacol 237 41 48 1:CAS:528:DC%2BD1MXls1Grur8%3D 19289138
109. A Poapolathep S Kumagai H Suzuki K Doi 2004 Development of early apoptosis and changes in T-cell subsets in mouse thymocyte primary cultures treated with nivalenol Exp Mol Pathol 77 149 152 1:CAS:528:DC%2BD2cXntlOht74%3D 15351239
110. DB Prelusky 1993 The effect of low-level deoxynivalenol on neurotransmitter levels measured in pig cerebral spinal fluid J Environ Sci Health B 28 731 761 1:STN:280:DyaK2c%2FpsFyjug%3D%3D 7903675
111. DB Prelusky 1994 The effect of deoxynivalenol on serotoninergic neurotransmitter levels in pig blood J Environ Sci Health B 29 1203 1218 1:STN:280:DyaK2M%2FotFCqtA%3D%3D 7527434
112. DB Prelusky HL Trenholm 1993 The efficacy of various classes of anti-emetics in preventing deoxynivalenol-induced vomiting in swine Nat Toxins 1 296 302 1:CAS:528:DyaK2cXhsFensLk%3D 8167950
113. DB Prelusky RG Gerdes KL Underhill BA Rotter PY Jui HL Trenholm 1994 Effects of low-level dietary deoxynivalenol on haematological and clinical parameters of the pig Nat Toxins 2 97 104 1:CAS:528:DyaK2cXlt1Ontbo%3D 8087437
114. DB Prelusky BA Rotter BK Thompson HL Trenholm 1997 Effect of the appetite stimulant cyproheptadine on deoxynivalenol-induced reductions in feed consumption and weight gain in the mouse J Environ Sci Health B 32 429 448 1:STN:280:DyaK2szitVWgsg%3D%3D 9177014
115. PH Rasmussen F Ghorbani T Berg 2003 Deoxynivalenol and other Fusarium toxins in wheat and rye flours on the Danish market Food Addit Contam 20 396 404 1:CAS:528:DC%2BD3sXjvVCltbY%3D 12775483
116. B Rio S Lautraite D Parent-Massin 1997 In vitro toxicity of trichothecenes on human erythroblastic progenitors Hum Exp Toxicol 16 673 679 1:CAS:528:DyaK2sXotV2gtr8%3D 9426370
117. S Robbana-Barnat B Loridon-Rosa H Cohen C Lafarge-Frayssinet GA Neish C Frayssinet 1987 Protein synthesis inhibition and cardiac lesions associated with deoxynivalenol ingestion in mice Food Addit Contam 4 49 56 1:CAS:528: DyaL2sXktVagsLg%3D 3556676
118. O Rocha K Ansari FM Doohan 2005 Effects of trichothecene mycotoxins on eukaryotic cells: a review Food Addit Contam 22 369 378 1:CAS:528: DC%2BD2MXkt1Srsrc%3D 16019807
119. RA Roth JR Harkema JP Pestka PE Ganey 1997 Is exposure to bacterial endotoxin a determinant of susceptibility to intoxication from xenobiotic agents? Toxicol Appl Pharmacol 147 300 311 1:CAS:528:DyaK1cXjt1Sgsw%3D%3D 9439725
120. BA Rotter BK Thompson M Lessard HL Trenholm H Tryphonas 1994 Influence of low-level exposure to Fusarium mycotoxins on selected immunological and hematological parameters in young swine Fundam Appl Toxicol 23 117 124 1:CAS:528:DyaK2cXlt1Oms7o%3D 7958555
121. BA Rotter BK Thompson RG Rotter 1994 Optimization of the mouse bioassay for deoxynivalenol as an alternative to large animal studies Bull Environ Contam Toxicol 53 642 647 1:CAS:528:DyaK2cXmt1ektrc%3D 7833598
122. BA Rotter DB Prelusky JJ Pestka 1996 Toxicology of deoxynivalenol (vomitoxin) J Toxicol Environ Health 48 1 34 1:CAS:528:DyaK28XjtFajt74%3D 8637056
123. M Schollenberger W Drochner M Rufle S Suchy H Terry-Jara HM Muller 2005 Trichothecene toxins in different groups of conventional and organic bread of the German market J Food Compos Anal 18 69 78 1:CAS:528:DC%2BD2cXhtVags7zN
124. RC Schothorst HP van Egmond 2004 Report from SCOOP task 3.2.10 "collection of occurrence data of Fusarium toxins in food and assessment of dietary intake by the population of EU member states"-Subtask: trichothecenes Toxicol Lett 153 133 143 1:CAS:528:DC%2BD2cXntlGltLs%3D 15342090
125. T Sergent M Parys S Garsou L Pussemier YJ Schneider Y Larondelle 2006 Deoxynivalenol transport across human intestinal Caco-2 cells and its effects on cellular metabolism at realistic intestinal concentrations Toxicol Lett 164 167 176 1:CAS:528:DC%2BD28XksVCqs7g%3D 16442754
126. YH Shi K Porter N Parameswaran HK Bae JJ Pestka 2009 Role of GRP78/BiP Degradation and ER Stress in deoxynivalenol-induced interleukin-6 upregulation in the macrophage Toxicol Sci 110 249 250 1:CAS:528:DC%2BD1MXnsFKktLs%3D
127. VI Shifrin P Anderson 1999 Trichothecene mycotoxins trigger a ribotoxic stress response that activates c-Jun N-terminal kinase and p38 mitogen-activated protein kinase and induces apoptosis J Biol Chem 274 13985 13992 1:CAS:528:DyaK1MXjsFWqsrw%3D 10318810
128. RL Sprando TFX Collins TN Black N Olejnik JI Rorie RM Eppley DI Ruggles 2005 Characterization of the effect of deoxynivalenol on selected male reproductive endpoints Food Chem Toxicol 43 623 635 1:CAS:528: DC%2BD2MXhtlOlsL4%3D 15721211
129. Y Sugita-Konishi JJ Pestka 2001 Differential upregulation of TNF-alpha, IL-6, and IL-8 production by deoxynivalenol (vomitoxin) and other 8-ketotrichothecenes in a human macrophage model J Toxicol Environ Health A 64 619 636 1:CAS:528:DC%2BD3MXptFGis7g%3D 11766169
130. I Szelenyi H Herold M Gothert 1994 Emesis induced in domestic pigs: a new experimental tool for detection of antiemetic drugs and for evaluation of emetogenic potential of new anticancer agents J Pharmacol Toxicol Methods 32 109 116 1:CAS:528:DyaK2MXitFens74%3D 7865862
131. A Thuvander T Moller HE Barbieri A Jansson AC Salomonsson M Olsen 2001 Dietary intake of some important mycotoxins by the Swedish population Food Addit Contam 18 696 706 1:CAS:528:DC%2BD3MXlsVOiur4%3D 11469326
132. JPY Ting JA Duncan Y Lei 2010 How the noninflammasome NLRs function in the innate immune system Science 327 286 290 1:CAS:528:DC%2BC3cXktlWktA%3D%3D 20075243
133. HL Trenholm RM Hamilton DW Friend BK Thompson KE Hartin 1984 Feeding trials with vomitoxin (deoxynivalenol)-contaminated wheat: effects on swine, poultry, and dairy cattle J Am Vet Med Assoc 185 527 531 1:CAS:528:DyaL2MXksFOg 6480467
134. AM Tritscher SW Page 2004 The risk assessment paradigm and its application for trichothecenes Toxicol Lett 153 155 163 1:CAS:528: DC%2BD2cXntlGltLk%3D 15342092
135. H Tryphonas F Iverson Y So EA Nera PF McGuire L O'Grady DB Clayson PM Scott 1986 Effects of deoxynivalenol (vomitoxin) on the humoral and cellular immunity of mice Toxicol Lett 30 137 150 1:CAS:528:DyaL28XkslCju7s%3D 3518157
136. AY Tsygankov SK Shore 2004 Src: regulation, role in human carcinogenesis and pharmacological inhibitors Curr Pharm Des 10 1745 1756 1:CAS:528: DC%2BD2cXktV2gsbg%3D 15180537
137. PC Turner VJ Burley JA Rothwell KLM White JE Cade CP Wild 2008 Dietary wheat reduction decreases the level of urinary deoxynivalenol in UK adults J Expo Sci Environ Epidemiol 18 392 399 1:CAS:528:DC%2BD1cXnt1Omt7s%3D 17940556
138. PC Turner EF Taylor KLM White JE Cade CP Wild 2009 A comparison of 24 h urinary deoxynivalenol with recent v. average cereal consumption for UK adults British J Nutr 102 1276 1284 1:CAS:528:DC%2BD1MXhsVyrtLzM
139. Ueno Y (1983) General toxicology. In: Ueno Y (ed) Trichothecenes: chemical, biological, and toxicological aspects. Elsevier, New York, pp 135-146
140. RL Uzarski JJ Pestka 2003 Comparative susceptibility of B cells with different lineages to cytotoxicity and apoptosis induction by translational inhibitors J Toxicol Environ Health A 66 2105 2118 1:CAS:528: DC%2BD3sXps1egsb0%3D 14710595
141. RL Uzarski Z Islam JJ Pestka 2003 Potentiation of trichothecene-induced leukocyte cytotoxicity and apoptosis by TNF-alpha and Fas activation Chem Biol Interact 146 105 119 1:CAS:528:DC%2BD3sXosVKqt7k%3D 14597125
142. S Van der Heyden J Goossens V Vandenbroucke G Vercauteren K Chiers F Pasmans F Haesebrouck P De Backer S Croubels R Ducatelle 2009 Reduced expression of intestinal P-glycoprotein following ingestion of deoxynivalenol (DON) contaminated feed in pigs J Comp Pathol 141 5
143. RF Vesonder A Ciegler AH Jensen 1973 Isolation of the emetic principle from Fusarium-infected corn Appl Microbiol 26 1008 1010 1:CAS:528: DyaE2cXls1yisw%3D%3D 4767291
144. KA Voss 2010 A new perspective on deoxynivalenol and growth suppression Toxicol Sci 113 281 283 1:CAS:528:DC%2BC3cXntlGmug%3D%3D 19933702
145. Williams BR (2001) Signal integration via PKR. SciSTKE 2001:RE2
146. SS Wong HR Zhou ML Marin-Martinez K Brooks JJ Pestka 1998 Modulation of IL-1beta, IL-6 and TNF-alpha secretion and mRNA expression by the trichothecene vomitoxin in the RAW 264.7 murine macrophage cell line Food Chem Toxicol 36 409 419 1:CAS:528:DyaK1cXktVCktrs%3D 9662416
147. S Wong RC Schwartz JJ Pestka 2001 Superinduction of TNF-alpha and IL-6 in macrophages by vomitoxin (deoxynivalenol) modulated by mRNA stabilization Toxicology 161 139 149 1:CAS:528:DC%2BD3MXisValsrY%3D 11295263
148. SS Wong HR Zhou JJ Pestka 2002 Effects of vomitoxin (deoxynivalenol) on the binding of transcription factors AP-1, NF-kappaB, and NF-IL6 in raw 264.7 macrophage cells J Toxicol Environ Health A 65 1161 1180 1:CAS:528: DC%2BD38Xmt1yru7g%3D 12167214
149. J Xu S Yang S Cai J Dong X Li Z Chen 2010 Identification of biochemical changes in lactovegetarian urine using 1H NMR spectroscopy and pattern recognition Anal Bioanal Chem 396 1451 1463 1:CAS:528:DC%2BD1MXhsFOnsbnP 20016880
150. GH Yang BB Jarvis YJ Chung JJ Pestka 2000 Apoptosis induction by the satratoxins and other trichothecene mycotoxins: relationship to ERK, p38 MAPK, and SAPK/JNK activation Toxicol Appl Pharmacol 164 149 160 1:CAS:528: DC%2BD3cXitl2qsLc%3D 10764628
151. GH Yang S Li JJ Pestka 2000 Down-regulation of the endoplasmic reticulum chaperone GRP78/BiP by vomitoxin (Deoxynivalenol) Toxicol Appl Pharmacol 162 207 217 1:CAS:528:DC%2BD3cXnsVWlsg%3D%3D 10652249
152. S Yazar GZ Omurtag 2008 Fumonisins, trichothecenes and zearalenone in cereals Int J Mol Sci 9 2062 2090 1:CAS:528:DC%2BD1cXhsVyhsbnL 19330061
153. T Yorimitsu DJ Klionsky 2005 Autophagy: molecular machinery for self-eating Cell Death Differ 12 2 1542 1552 1:CAS:528:DC%2BD2MXhtFCjt7%2FJ 16247502
154. N Yoshino M Takizawa H Akiba H Okumura F Tashiro M Honda Y Ueno 1996 Transient elevation of intracellular calcium ion levels as an early event in T-2 toxin-induced apoptosis in human promyelotic cell line HL-60 Nat Toxins 4 234 241 1:CAS:528:DyaK2sXot1Km 8946399
155. Yoshizawa T (1983) Trichothecenes-chemical, biological, and toxicological aspects. In: Ueno Y (ed) Dev, Food Sci. Red-mold diseases and natural occurence in Japan. Kodansha Ltd., Tokyo, pp 195-209
156. T Yoshizawa N Morooka 1973 Deoxynivalenol and its monoacetate: new mycotoxins from Fusaruium roseum and moldy barley Agric Biol Chem 37 2933 2934 1:CAS:528:DyaE2cXkt1aru7s%3D
157. LG Young L McGirr VE Valli JH Lumsden A Lun 1983 Vomitoxin in corn fed to young pigs J Anim Sci 57 655 664 1:CAS:528:DyaL3sXltlyhurg%3D 6630099
158. HR Zhou D Yan JJ Pestka 1997 Differential cytokine mRNA expression in mice after oral exposure to the trichothecene vomitoxin (deoxynivalenol): dose response and time course Toxicol Appl Pharmacol 144 294 305 1:CAS:528: DyaK2sXjsl2ltb8%3D 9194413
159. HR Zhou D Yan JJ Pestka 1998 Induction of cytokine gene expression in mice after repeated and subchronic oral exposure to vomitoxin (Deoxynivalenol): differential toxin-induced hyporesponsiveness and recovery Toxicol Appl Pharmacol 151 347 358 1:CAS:528:DyaK1cXls1Snt78%3D 9707511
160. HR Zhou JR Harkema D Yan JJ Pestka 1999 Amplified proinflammatory cytokine expression and toxicity in mice coexposed to lipopolysaccharide and the trichothecene vomitoxin (deoxynivalenol) J Toxicol Environ Health 57 115 136 1:CAS:528:DyaK1MXjt1yisLs%3D
161. HR Zhou JR Harkema JA Hotchkiss D Yan RA Roth JJ Pestka 2000 Lipopolysaccharide and the trichothecene vomitoxin (deoxynivalenol) synergistically induce apoptosis in murine lymphoid organs Toxicol Sci 53 253 263 1:CAS:528:DC%2BD3cXhtF2ks78%3D 10696773
162. HR Zhou Z Islam JJ Pestka 2003 Kinetics of lipopolysaccharide-induced transcription factor activation/inactivation and relation to proinflammatory gene expression in the murine spleen Toxicol Appl Pharmacol 187 147 161 1:CAS:528:DC%2BD3sXitlWnsbY%3D 12662898
163. HR Zhou Z Islam JJ Pestka 2003 Rapid, sequential activation of mitogen-activated protein kinases and transcription factors precedes proinflammatory cytokine mRNA expression in spleens of mice exposed to the trichothecene vomitoxin Toxicol Sci 72 130 142 1:CAS:528:DC%2BD3sXit1yrsrs%3D 12604842
164. HR Zhou AS Lau JJ Pestka 2003 Role of double-stranded RNA-activated protein kinase R (PKR) in deoxynivalenol-induced ribotoxic stress response Toxicol Sci 74 335 344 1:CAS:528:DC%2BD3sXlsl2kuro%3D 12773753
165. HR Zhou Z Islam JJ Pestka 2005 Induction of competing apoptotic and survival signaling pathways in the macrophage by the ribotoxic trichothecene deoxynivalenol Toxicol Sci 87 113 122 1:CAS:528:DC%2BD2MXovVOjsLY%3D 15976193
166. HR Zhou Q Jia JJ Pestka 2005 Ribotoxic stress response to the trichothecene deoxynivalenol in the macrophage involves the SRC family kinase Hck Toxicol Sci 85 916 926 1:CAS:528:DC%2BD2MXksVSjt70%3D 15772366