Advertisement

Toxicology of mycotoxins

  • Robert R. M. Paterson
  • Nelson Lima
Part of the Experientia Supplementum book series (EXS, volume 100)

Abstract

Humans are exposed to mycotoxins via ingestion, contact and inhalation. This must have occurred throughout human history and led to severe outbreaks. Potential diseases range from akakabio-byo to stachybotryotoxicosis and cancer. The known molecular bases of toxicology run the gamut of 23 compounds, from aflatoxins (AFs) to zearalenone, ochratoxin A and deoxynivalenol. Ergotism is one of the oldest recognized mycotoxicosis, although mycotoxin science only commenced in the 1960s with the discovery of AFs in turkey feed. AFs are carcinogenic. Some others are suspected carcinogens. The effects of mycotoxins are acute or chronic in nature. Mycotoxins are well known in the scientific community, although they have a low profile in the general population. An incongruous situation occurs in United States where mycotoxins from “moldy homes” are considered to be a significant problem, although there is a general debate about seriousness. This contrasts with the thousands of deaths from mycotoxins that occur, even now, in the technologically less developed countries (e.g., Indonesia, China, and Africa). Mycotoxins are more toxic than pesticides. Studies are moving from whole animal work to investigating the biochemical mechanisms in isolated cells, and the mechanisms of toxicity at the molecular level are being elucidated. The stereochemical nature of AFs has been shown to be important. In addition, the effect of multiple mycotoxins is being increasingly investigated, which will more accurately represent the situation in nature. It is anticipated that more fungal metabolites will be recognized as dangerous toxins and permitted statutory levels will decrease in the future.

Keywords

Allergy Clin Immunol Fusarium Moniliforme Cyclopiazonic Acid Trichothecene Mycotoxin Food Chem Toxicol 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Hawksworth DL (2001) The magnitude of fungal diversity: The 1.5 million species estimate revisited. Mycol Res 105: 1422–1432CrossRefGoogle Scholar
  2. 2.
    CAST (2003) Mycotoxins: Risks in Plant, Animal, and Human Systems. Council for Agricultural Science and Technology, Ames, IAGoogle Scholar
  3. 3.
    Marr JS, Malloy CD (1996) An epidemiologic analysis of the ten plagues of Egypt. Caduceus 12: 7–24PubMedGoogle Scholar
  4. 4.
    Paterson RRM (2006) Fungi and fungal toxins as weapons. Mycol Res 110: 1003–1010PubMedCrossRefGoogle Scholar
  5. 5.
    Lewis L, Onsongo M, Njapau H, Schurz-Rogers H, Luber G, Kieszak S, Nyamongo J, Backer L, Dahiye A, Misore A, DeCock K, Rubin C (2005) Aflatoxin contamination of commercial maize products during an outbreak of acute aflatoxicosis in Eastern and Central Kenya. Environ Health Perspect 113: 1763–1767PubMedCrossRefGoogle Scholar
  6. 6.
    Cole RJ, Jarvis BB, Schweikert MA (2003) Handbook of Secondary Fungal Metabolites, 3 Vols, Academic Press, The NetherlandsGoogle Scholar
  7. 7.
    Klaassen CD, Eaton DL (1991) Principles of Toxicology. In: MO Amdur, J Doull, CD Klaassen (eds): Casarett and Doull’s Toxicology. The Basic Science of Poisons. Pergamon Press, New York, 12–49Google Scholar
  8. 8.
    IARC (1993) Monographs on the Evaluation of Carcinogenic Risks to Humans, Some Naturally Occurring Substances: Food Items and Constituents, Heterocyclic Aromatic Amines, and Mycotoxins. International Agency for Research on Cancer, Lyon, 56, 489–521Google Scholar
  9. 9.
    Krishnamachari KAVR, Bhat RV, Nagarajan V, Tilak TBG (1975) Hepatitis due to aflatoxicosis. An outbreak in Western India. Lancet 1: 1061–1063PubMedCrossRefGoogle Scholar
  10. 10.
    Ngindu A, Johnson BK, Kenya PR, Ngira JA, Ocheng DM, Nandwa H, Omondi TN, Jansen AJ, Ngare W, Kaviti JN, Gatei D, Siongok TA (1982) Outbreak of acute hepatitis caused by aflatoxin poisoning in Kenya. Lancet 1: 1346–1348PubMedCrossRefGoogle Scholar
  11. 11.
    Hendrickse RG (1984) The influence of aflatoxins on child health in the tropics with particular reference to kwashiorkor. Trans R Soc Trop Med Hyg 78: 427–435PubMedCrossRefGoogle Scholar
  12. 12.
    Henry SH, Bosch FX, Troxell TC, Bolger PM (1999) Reducing liver cancer — Global control of aflatoxin. Science 286: 2453–2454.PubMedCrossRefGoogle Scholar
  13. 13.
    Autrup H, Bradley KA, Shamsuddin AKM, Wakhisi J, Wasunna A (1983) Detection of putative adduct with fluorescence characteristics identical to 2,3-dihydro-2-(7′-guanyl)-3-hydroxyaflatoxin B1 in human urine collected in Murang’a district, Kenya. Carcinogenesis 4: 1193–1195PubMedCrossRefGoogle Scholar
  14. 14.
    Yeh FS, Yu MC, Mo CC, Luo S, Tong MJ, Henderson BE (1989) Hepatitis B virus, aflatoxins, and hepatocellular carcinoma in southern Guangxi, China. Cancer Res 49: 2506–2509PubMedGoogle Scholar
  15. 15.
    Campbell TC, Chen J, Liu C, Li J, Parpia B (1990) Nonassociation of aflatoxin with primary liver cancer in a cross-sectional ecological survey in the People’s Republic of China. Cancer Res 50: 6882–6893PubMedGoogle Scholar
  16. 16.
    Odhav B, Adam JK, Bhoola KD (2008) Modulating effects of fumonisin B1 and ochratoxin A on leukocytes and messenger cytokines of the human immune system. Int Immunopharmacol 8: 799–809PubMedCrossRefGoogle Scholar
  17. 17.
    Joffe ZA, Yagen B (1977) Comparative study of the yield of T-2 toxic produced by Fusarium poae, F. sporotrichioides and F. sporotrichioides var. tricinctum strains from different sources. Mycopathologia 60: 93–97PubMedCrossRefGoogle Scholar
  18. 18.
    Ueno Y (1984) Toxicological features of T-2 toxin and related trichothecenes. Fund Appl Toxicol 4: S124–132CrossRefGoogle Scholar
  19. 19.
    Yeno Y (1985) The toxicology of mycotoxins. Crit Rev Toxicol 14: 99–132CrossRefGoogle Scholar
  20. 20.
    Bucheli TD, Wettstein FE, Hartmann N, Erbs M, Vogelgsang S, Forrer HR, Schwarzenbach RP (2008) Fusarium mycotoxins: Overlooked aquatic micropollutants? J Agric Food Chem 56: 1029–1034PubMedCrossRefGoogle Scholar
  21. 21.
    Painter K (1997) Puberty signs evident in 7-and 8-year old girls. USA Today, April 8, A–1Google Scholar
  22. 22.
    Hsieh DPH (1989) Potential human health hazards of mycotoxins. In: S Natori, K Hashimoto, Y Ueno (eds): Mycotoxins and Phycotoxins 1988. Elsevier, The Netherlands, 69–80Google Scholar
  23. 23.
    Szuets P, Mesterhazy A, Falkay G, Bartok T (1997) Early thelarche symptoms in children and their relations to zearalenone contamination in foodstuffs. Cereal Res Commun 25: 429–436Google Scholar
  24. 24.
    Gelderblom WCA, Thiel PG, van Der Merwe KJ (1988) The role of rat liver microsomal enzymes in the metabolism of the fungal metabolite, fusarin C. Food and Chemical Toxicology. Food Chem Toxicol 26: 31–36PubMedCrossRefGoogle Scholar
  25. 25.
    Zhu B, Jeffrey AM (1992) Stability of fusarin C: Effects of the normal cooking procedure used in China and pH. Nutr Cancer 18: 53–58PubMedCrossRefGoogle Scholar
  26. 26.
    Li M, Lu S, Jin C, Wang Y, Wang M, Cheng S, Tian G (1980) Experimental studies on the carcinogenicity of fungus contaminated food from Linxian County. In: HV Gelboin (ed.): Genetic and Environmental Factors in Experimental Human Cancer. Japan Science Society Press, Tokyo, 139–148Google Scholar
  27. 27.
    Marasas WFO (1996) Fumonisins: History, world-wide occurrence and impact. In: LS Jackson, JW DeVries, LB Bullerman (eds): Fumonisins in Food. Plenum Press, New York, 1–17Google Scholar
  28. 28.
    Franceschi S, Bidoli E, Baron AE, La Vecchia C (1990) Maize and risk of cancers of the oral cavity, pharynx, and esophagus in northeastern Italy. J Natl Cancer Inst 82: 1407–1411PubMedCrossRefGoogle Scholar
  29. 29.
    Gelderblom WCA, Jaskiewicz K, Marasas WFO, Thiel PG, Horak RM, Vleggaar R, Kriek, NPJ (1988) Pumonisins — Novel mycotoxins with cancer-promoting activity produced by Fusarium moniliforme. Appl Environ Microbiol 54: 1806–1811PubMedGoogle Scholar
  30. 30.
    Frisvad JC, Smedsgaard J, Samson RA, Larsen TO, Thrane U (2007) Fumonisin B2 production by Aspergillus niger. J Agric Food Chem 55: 9727–9732PubMedCrossRefGoogle Scholar
  31. 31.
    Tolleson WH, Melchior WB Jr, Morris SM, McGarrity LJ, Domon OE, Muskhelishvili L, Sjill J, Howard PC (1996) Apoptotic and anti-proliferative effects of fumonisin B1 in human keratinocytes, fibroblasts, esophageal epithelial cells and hepatoma cells. Carcinogenesis 17: 239–249PubMedCrossRefGoogle Scholar
  32. 32.
    Forgacs J (1972) Stachybotryotoxicosis. In: S Kadis, A Ceigler, S Ajl (eds): Micoobial Toxins. Volume VIII. Academic Press, New York, 95–128Google Scholar
  33. 33.
    Dearborn DG, Yike I, Sorenson WG, Miller MJ, Etzel RA (1999) Overview of investigations into pulmonary hemorrhage among infants in Cleveland, Ohio. Environ Health Perspect 107: 495–499PubMedCrossRefGoogle Scholar
  34. 34.
    Ueno Y (1974) Citreoviridin from Penicillium citreoviride Biourge. In: IFH Purchase (ed.): Mycotoxins. Elsevier, New York, 283–302Google Scholar
  35. 35.
    Beardall JM, Miller JD (1994) Diseases in humans with mycotoxins as possible causes. In: JD Miller, HL Trenholm (eds): Mycotoxins in Grains: Compounds Other than Aflatoxins. Eagan Press, MN, 487–539Google Scholar
  36. 36.
    Demeke T, Kidane Y, Wuhib E (1979) Ergotism — A report on an epidemic, 1977–78. Ethiop Med J 17: 107–113PubMedGoogle Scholar
  37. 37.
    Krishnamachari KAVR, Bhat RV (1976) Poisoning by ergoty bajra (pearl millet) in man. Indian J Med Res 64: 1624–1628PubMedGoogle Scholar
  38. 38.
    Richard JL (1991) Mycotoxins as immunomodulators in animal systems. In: GA Bray, DH Ryan (eds): Mycotoxins, Cancer, and Health. Pennington Center Nutrition Series, Louisiana State University Press, LA, 197–220Google Scholar
  39. 39.
    Krogh P (1976) Epidemiology of mycotoxic porcine nephropathy. Nord Vet Med 28: 452–458PubMedGoogle Scholar
  40. 40.
    Prelusky DB, Hamilton RMG, Trenholm HL, Miller JD (1986) Tissue distribution and excretion of radioactivity following administration of 14C-labeled deoxynivalenol to white leghorn hens. Fundam Appl Toxicol 7: 635–645PubMedCrossRefGoogle Scholar
  41. 41.
    Bryden WL (1991) Occurrence and biological effects of cyclopiazonic acid. In: K Mixe, JL Richard (eds): Emerging Problem Resulting from Microbial Contamination. National Institute of Hygienic Science, Tokyo, 127–147Google Scholar
  42. 42.
    Pier AC (1986) Immunomodulation in aflatoxicosis. In: JL Richard, JR Thurston (eds): Diagnosis of Mycotoxicoses. Martinus Nijhoff Publishers, The Netherlands, 143–148Google Scholar
  43. 43.
    Kadian SK, Monga DP, Goel MC (1988) Effect of aflatoxin B1 on the delayed type hypersensitivity and phagocytic activity of reticuloendothelial system in chickens. Mycopathologia 104: 33–36PubMedCrossRefGoogle Scholar
  44. 44.
    Robbana-Barnat S, Lafarge-Frayssinet C, Cohen H, Neish GA, Frayssinet C (1988) Immunosuppressive properties of deoxynivalenol. Toxicology 48: 155–166PubMedCrossRefGoogle Scholar
  45. 45.
    Burns RB, Dwivedi P (1986) The natural occurrence of ochratoxin A and its effects in poultry. A review. Part II. Pathology and immunology. World’s Poultry Sci J 42: 48–55CrossRefGoogle Scholar
  46. 46.
    Escoula L, Thomsen M, Bourdiol D, Pipy B, Peuriere S, Roubinet F (1988) Patulin immunotoxicology: Effect on phagocyte activation and the cellular and humoral immune system of mice and rabbits. Int J Immunopharmacol 10: 983–989PubMedCrossRefGoogle Scholar
  47. 47.
    McKinley ER, Carlton WW, Boon GD (1982) Patulin mycotoxicosis in the rat: Toxicology, pathology and clinical pathology. Food Chem Toxicol 20: 289–300PubMedCrossRefGoogle Scholar
  48. 48.
    Dawe DL, Stuedemann JA, Hill NS, Thompson FN (1997) Immunosuppression in cattle with fescue toxicosis. In: CW Bacon, NS Hill (eds): Neotyphodium/Grass Interactions. Plenum Press, New York, 411–412Google Scholar
  49. 49.
    Dietert RR, Bloom SE, Qureshi MA, Nanna UC (1983) Hematological toxicology following embryonic exposure to aflatoxin B1. Proc Soc Exp Biol Med 173: 481–485PubMedGoogle Scholar
  50. 50.
    Segal R, Milo Goldzweig I, Joffe AZ, Yagen B (1983) Trichothecene-induced hemolysis. 1. The hemolytic activity of T-2 toxin. Toxicol Appl Pharmacol 70: 343–349PubMedCrossRefGoogle Scholar
  51. 51.
    Richard JL (1998) Mycotoxins, toxicity and metabolism in animals — A systems approach overview. In: M Miraglia, H van Egmond, C Brera, J Gilbert (eds): Mycotoxins and Phycotoxins — Developments in Chemistry, Toxicology and Food Safety. Alaken Inc, CO, 363–397Google Scholar
  52. 52.
    Edgar JA, Culvenor CCJ (1985) Aspects of the structure of phomopsin A, the mycotoxin causing lupinosis. In: AA Seawright, MP Hegarty, LF James, RF Keeler (eds): Plant Toxicology. Queensland Poisonous Plants Committee, Yeerongpilly, Australia, 589–594Google Scholar
  53. 53.
    Voss KA, Chamberlain WJ, Bacon CW, Herbert RA, Walters DB, Norred WP (1995) Subchronic feeding study of the mycotoxin fumonisin B1 in B6C3F1 mice and Fischer 344 rats. Fund Appl Toxicol 24: 102–110CrossRefGoogle Scholar
  54. 54.
    Hagler WM Jr, Towers NR, Mirocha CJ, Eppley RM, Bryden WL (2001) Zearalenone: Mycotoxin or mycoestrogen? In: BA Summerell, JF Leslie, D Backhouse, WL Bryden, LW Burgess (eds): Fusarium: Paul E. Nelson Memorial Symposium. APS Press, MN, 321–331Google Scholar
  55. 55.
    Hunt JN (1980) A possible relation between the regulation of gastric emptying and food intake. J Physiol 239: 61–64Google Scholar
  56. 56.
    Norred WP, Voss KA (1994) Toxicity and role of fumonisins in animal diseases and human esophageal cancer. J Food Protect 57: 522–527Google Scholar
  57. 57.
    Marasas, WFO, Nelson PE (1987) Mycotoxicology. Pennsylvania State University Press, PAGoogle Scholar
  58. 58.
    Eaton DL, Groopman JD (1994) The Toxicology of Aflatoxins: Human Health, Veterinary and Agricultural Significance. Academic Press, New YorkGoogle Scholar
  59. 59.
    Gelderblom WCA, Cawood ME, Snyman D, Vleggaar R, Marasas WFO (1993) Structure-activity relationships of fumonisins in short-term carcinogenesis and cytotoxicity studies. Food Chem Toxicol 31: 407–414PubMedCrossRefGoogle Scholar
  60. 60.
    Riley RT, Showker JL (1991) The mechanism of patulin’s cytotoxicity and the antioxidant activity of indole tetramic acids. Toxicol Appl Pharmacol 109: 108–126PubMedCrossRefGoogle Scholar
  61. 61.
    Paterson RRM (2008) Fungal enzyme inhibitors as pharmaceuticals, toxins, and scourge of PCR. Curr Enzyme Inhib 4: 46–59CrossRefGoogle Scholar
  62. 62.
    Paterson RRM, Lima N (2009) Mutagens manufactured in fungal culture may affect DNA/RNA of producing fungi. J Appl Microbiol 106: 1070–1080PubMedCrossRefGoogle Scholar
  63. 63.
    Luch A (2008) The mode of action of organic carcinogens on cellular structures. In: LP Bignold (ed.): Cancer: Cell Structures, Carcinogens and Genomic Instability. Birkhäuser, Switzerland 65–95Google Scholar
  64. 64.
    Groopman JD, Kensler TW (2005) Role of metabolism and viruses in aflatoxin-induced liver cancer. Toxicol Appl Pharmacol 206: 131–137PubMedCrossRefGoogle Scholar
  65. 65.
    Groopman JD, Johnson D, Kensler TW (2005) Aflatoxin and hepatitis B virus biomarkers: A paradigm for complex environmental exposures and cancer risk. Cancer Biomark 1: 5–14PubMedGoogle Scholar
  66. 66.
    Faridha A, Faisal K, Akbarsha MA (2007) Aflatoxin treatment brings about generation of multinucleate giant spermatids (symplasts) through opening of cytoplasmic bridges: Light and transmission electron microscopic study in Swiss mouse. Reprod Toxicol 24: 403–408PubMedCrossRefGoogle Scholar
  67. 67.
    Palma N, Cinelli S, Sapora O, Wilson SH, Dogliotti E (2007) Ocharatoxin A-induced mutagenesis in mammalian cells is consistent with the production of oxidative stress. Chem Res Toxicol 20: 1031–1037PubMedCrossRefGoogle Scholar
  68. 68.
    Rached E, Hoffmann D, Blumbach K, Weber K, Dekant W, Mally A (2008) Evaluation of putative biomarkers of nephrotoxicity after exposure to ochratoxin A in vivo and in vitro. Toxicol Sci 103: 371–381PubMedCrossRefGoogle Scholar
  69. 69.
    Mantle PG, Nagy JM (2008) Binding of ochratoxin A to a urinary globulin: A new concept to account for gender difference in rat nephrocarcinogenic responses. Int J Mol Sci 9: 719–735PubMedCrossRefGoogle Scholar
  70. 70.
    Assaf H, Azouri H, Pallardy M (2004) Ochratoxin A induces apoptosis in human lymphocytes through down regulation of Bcl-xL. Toxicol Sci 79: 335–344PubMedCrossRefGoogle Scholar
  71. 71.
    Schumacher DM, Müller C, Metzler M, Lehmann L (2006) DNA-DNA cross-links contribute to the mutagenic potential of the mycotoxin patulin. Toxicol Lett 166: 268–275PubMedCrossRefGoogle Scholar
  72. 72.
    Tsuda S, Kosaka Y, Murakami M, Matsuo H, Matsusaka N, Taniguchi K, Sasaki YF (1998) Detection of nivalenol genotoxicity in cultured cells and multiple mouse organs by the alkaline single-cell gel electrophoresis assay. Mutat Res 415: 191–200PubMedGoogle Scholar
  73. 73.
    Bony S, Olivier-Loiseau L, Carcelen M, Devaux A (2007) Genotoxic potential associated with low levels of the Fusarium mycotoxins nivalenol and fusarenon X in a human intestinal cell line. Toxicol In Vitro 21: 457–465PubMedCrossRefGoogle Scholar
  74. 74.
    Wang JS, Groopman JD (1999) DNA damage by mycotoxins. Mutat Res 424: 167–181PubMedGoogle Scholar
  75. 75.
    Gelderblom WCA, Thiel PG, van der Merwe KJ (1984) Metabolic activation and deactivation of fusarin C, a mutagen produced by Fusarium moniliforme. Biochem Pharmacol 33: 1601–1603PubMedCrossRefGoogle Scholar
  76. 76.
    Prelusky DB (1996) A study on the effect of deoxynivalenol on serotonin receptor binding in pig brain membranes. J Environ Sci Health B 31: 1103–1117PubMedCrossRefGoogle Scholar
  77. 77.
    Prelusky DB, Trenholm HL (1993) The efficacy of various classes of anti-emetics in preventing deoxynivalenol-induced vomiting in swine. Nat Toxins 1: 296–302PubMedCrossRefGoogle Scholar
  78. 78.
    Prelusky DB (1993) The effect of low-level deoxynivalenol on neurotransmitter levels measured in pig cerebral spinal fluid. J Environ Sci Health B 28: 731–761PubMedCrossRefGoogle Scholar
  79. 79.
    Bondy GS, Pestka JJ (2000) Immunomodulation by fungal toxins. J Toxicol Environ Health B 3: 109–143CrossRefGoogle Scholar
  80. 80.
    Wong SS, Zhou HR, Marin-Martinez ML, Brooks K, Pestka JJ (1998) Modulation of IL-1β, IL-6 and TNF-α secretion and mRNA expression by the trichothecene vomitoxin in the RAW 264.7 murine macrophage cell line. Food Chem Toxicol 36: 409–419PubMedCrossRefGoogle Scholar
  81. 81.
    Yan D, Zhou HR, Brooks KH, Pestka JJ (1998) Role of macrophages in elevated IgA and IL-6 production by Peyer’s patch cultures following acute oral vomitoxin exposure. Toxicol Appl Pharmacol 148: 261–273PubMedCrossRefGoogle Scholar
  82. 82.
    Pestka JJ, Yon D, King LE (1994) Flow cytometric analysis of the effects of in vitro exposure to vomitoxin (deoxynivalenol) on apoptosis in murine T, B and IgA+ cells. Food Chem Toxicol 32: 1125–1136PubMedCrossRefGoogle Scholar
  83. 83.
    Islam Z, King LE, Fraker PJ, Pestka JJ (2003) Differential induction of glucocorticoid-dependent apoptosis in murine lymphoid subpopulations in vivo following coexposure to lipopolysaccharide and vomitoxin (deoxynivalenol). Toxicol Appl Pharmacol 187: 69–79PubMedCrossRefGoogle Scholar
  84. 84.
    Islam Z, Pestka JJ (2003) Role of IL-1β in endotoxin potentiation of deoxynivalenol-induced corticosterone response and leukocyte apoptosis in mice. Toxicol Sci 74: 93–102PubMedCrossRefGoogle Scholar
  85. 85.
    Ueno Y (1983) Trichothecenes: Chemical, biological, and toxicological aspects. In: Y Ueno (ed.): Trichothecenes. Elsevier Press, Amsterdam, 135–146Google Scholar
  86. 86.
    Pestka JJ, Smolinski AT (2005) Deoxynivalenol: Toxicology and potential effects on humans. J Toxicol Environ Health B Crit Rev 8: 39–69PubMedGoogle Scholar
  87. 87.
    Yang GH, Jarvis BB, Chung YJ, Pestka JJ (2000) Apoptosis induction by the satratoxins and other trichothecene mycotoxins: Relationship to ERK, p38 MAPK, and SAPK/JNK activation. Toxicol Appl Pharmacol 164: 149–160PubMedCrossRefGoogle Scholar
  88. 88.
    Zhou HR, Islam Z, Pestka JJ (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: 130–142PubMedCrossRefGoogle Scholar
  89. 89.
    Zhou HR, Jia Q, Pestka JJ (2005) Ribotoxic stress response to the trichothecene deoxynivalenol in the macrophage involves the Src family kinase Hck. Toxicol Sci 85: 916–926PubMedCrossRefGoogle Scholar
  90. 90.
    Zhou HR, Lau AS, Pestka JJ (2003) Role of double-stranded RNA-activated protein kinase R (PKR) in deoxynivalenol-induced ribotoxic stress response. Toxicol Sci 74: 335–344PubMedCrossRefGoogle Scholar
  91. 91.
    Pestka JJ, Zhou HR (2003) Hck-and PKR-dependent mitogen-activated protein kinase phosphorylation and AP-1, C/EBP and NF-κB activation precedes deoxynivalenol-induced TNF-α and MIP-2 expression. Toxicologist 72: 121Google Scholar
  92. 92.
    Rizzo AF, Atroshi F, Ahotupa M, Sankari S, Elovaara E (1994) Protective effect of antioxidants against free radical-mediated lipid peroxidation induced by DON or T-2 toxin. Zentralbl Veterinärmed A 41: 81–90PubMedGoogle Scholar
  93. 93.
    Sun XM, Zhang XH, Wang HY, Cao WJ, Yan X, Zuo LF, Wang JL, Wang FR (2002) Effects of sterigmatocystin, deoxynivalenol and aflatoxin G1 on apoptosis of human peripheral blood lymphocytes in vitro. Biomed Environ Sci 15: 145–152PubMedGoogle Scholar
  94. 94.
    Gray JS, Pestka JJ (2007) Transcriptional regulation of deoxynivalenol-induced IL-8 expression in human monocytes. Toxicol Sci 99: 502–511PubMedCrossRefGoogle Scholar
  95. 95.
    Li M, Pestka JJ (2008) Comparative induction of 28S ribosomal RNA cleavage by ricin and the trichothecenes deoxynivalenol and T-2 toxin in the macrophage. Toxicol Sci 105: 67–78PubMedCrossRefGoogle Scholar
  96. 96.
    Malekinejad H, Schoevers EJ, Daemen IJJM, Zijlstra C, Colenbrander B, Fink-Gremmels J, Ro BAJ (2007) Exposure of oocytes to the Fusarium toxins zearalenone and deoxynivalenol causes aneuploidy and abnormal embryo development in pigs. Biol Reprod 77: 840–847PubMedCrossRefGoogle Scholar
  97. 97.
    Knasmuller S, Bresgen N, Kassie F, Mersch-Sundermann V, Gelderblom W, Zohrer E, Eckl PM (1997) Genotoxic effects of three Fusarium mycotoxins, fumonisin B1, moniliformin and vomitoxin in bacteria and in primary cultures of rat hepatocytes. Mutat Res 391: 39–48PubMedGoogle Scholar
  98. 98.
    Wang E, Norred WP, Bacon CW, Riley RT, Merrill AH Jr (1991) Inhibition of sphingolipid biosynthesis by fumonisins: Implications for diseases associated with Fusarium moniliforme. J Biol Chem 266: 14486–14490PubMedGoogle Scholar
  99. 99.
    Sorenson WG, Simpson J, Castranova V (1985) Toxicity of the mycotoxin patulin for rat peritoneal macrophages. Environ Res 38: 407–416PubMedCrossRefGoogle Scholar
  100. 100.
    Bourdiol D, Escoula L, Salvayre R (1990) Effect of patulin on microbicidal activity of mouse peritoneal macrophages. Food Chem Toxicol 28: 29–33PubMedCrossRefGoogle Scholar
  101. 101.
    Knaus HG, McManus OB, Lee SH, Schmalhofer WA, Garcia-Calvo M, Helms LMH, Sanchez M, Giangiacomo K, Reuben JP, Smith AB, Kaczorowski GJ, Garcia ML (1994) Tremorgenic indole alkaloids potently inhibit smooth muscle high-conductance calcium-activated potassium channels. Biochemistry 33: 5819–5828PubMedCrossRefGoogle Scholar
  102. 102.
    Gallagher RT, Richard JL, Stahr HM, Cole RJ (1978) Cyclopiazonic acid production by aflatoxigenic and nonaflatoxigenic strains of Aspergillus flavus. Mycopathologia 66: 31–36PubMedCrossRefGoogle Scholar
  103. 103.
    Dvorak R, Jagos J, Bouda J, Piskac A, Zapletal O (1977) Changes in the clinico-biochemical indices in the rumen liquor and urine in cases of experimental aflatoxicosis in dairy cows. Vet Med (Prague) 22: 161–169Google Scholar
  104. 104.
    Tung HT, Donaldson WE, Hamilton PB (1972) Altered lipid transport during aflatoxicosis. Toxicol Appl Pharmacol 22: 97–104PubMedCrossRefGoogle Scholar
  105. 105.
    Osborne DJ, Hamilton PB (1981) Decreased pancreatic digestive enzymes during aflatoxicosis. Poultry Sci 60: 1818–1821Google Scholar
  106. 106.
    Bush RK, Portnoy JM, Saxon A, Terr AI, Wood RA (2006) The medical effects of mold exposure. J Allergy Clin Immunol 117: 326–333PubMedCrossRefGoogle Scholar
  107. 107.
    Wood RA, Bush RK (2006) Reply. J Allergy Clin Immunol 118: 767CrossRefGoogle Scholar
  108. 108.
    Lieberman A, Rea W, Curtis L (2006) Adverse health effects of indoor mold exposure. J Allergy Clin Immunol 118: 763PubMedCrossRefGoogle Scholar
  109. 109.
    Strickland MHV (2006) How solid is the Academy position paper on mold exposure? J Allergy Clin Immunol 118: 763–764PubMedCrossRefGoogle Scholar
  110. 110.
    Hardin BD, Kelman BJ, Saxon A (2007) Reply. J Allergy Clin Immunol 119: 256–257PubMedCrossRefGoogle Scholar
  111. 111.
    Bouslimi A, Bouaziz C, Ayed-Boussema I, Hassen W, Bacha H (2008) Individual and combined effects of ochratoxin A and citrinin on viability and DNA fragmentation in cultured Vero cells and on chromosome aberrations in mice bone marrow cells. Toxicology 251: 1–7PubMedCrossRefGoogle Scholar
  112. 112.
    Orsi RB, Oliveira CAF, Dilkin P, Xavier JG, Direito GM, Corrêa B (2007) Effects of oral administration of aflatoxin B1 and fumonisin B1 in rabbits (Oryctolagus cuniculus). Chem Biol Interact 170: 201–208PubMedCrossRefGoogle Scholar
  113. 113.
    Tammer B, Lehmann I, Nieber K, Altenburger R (2007) Combined effects of mycotoxin mixtures on human T cell function. Toxicol Lett 170: 124–133PubMedCrossRefGoogle Scholar
  114. 114.
    Klarić MŠ, Pepeljnjak S, Domijan AM, Petrik J (2007) Lipid peroxidation and glutathione levels in porcine kidney PK15 cells after individual and combined treatment with fumonisin B1, beauvericin and ochratoxin A. Basic Clin Pharmacol Toxicol 100: 157–164PubMedCrossRefGoogle Scholar
  115. 115.
    Heussner AH, Dietrich DR, O’Brien E (2006) In vitro investigation of individual and combined cytotoxic effects of ochratoxin A and other selected mycotoxins on renal cells. Toxicol In Vitro 20: 332–341PubMedCrossRefGoogle Scholar
  116. 116.
    Paterson RRM, Lima N (2009) How will climate change affect mycotoxins in food. Food Res Int, in press Google Scholar

Copyright information

© Birkhäuser Verlag/Switzerland 2010

Authors and Affiliations

  • Robert R. M. Paterson
    • 1
  • Nelson Lima
    • 1
  1. 1.Centre of Biological Engineering, IBB-Institute for Biotechnology and BioengineeringUniversidade do MinhoBragaPortugal

Personalised recommendations