Mycotoxin Research

, 23:152 | Cite as

Alternaria toxins: DNA strand-breaking activity in mammalian cellsin vitro

  • E. Pfeiffer
  • S. Eschbach
  • M. Metzler


Treatment, for 1 h, of cultured Chinese hamster V79 cells, human liver HepG2 cells, and human colon HT-29 cells with theAlternaria toxins alternariol (AOH) and alternariol methyl ether (AME) caused a concentration-dependent induction of DNA strand breaks at concentrations ranging from 5 to 50 micromolar. After treatment for 24 h, DNA strand breaks were observed in HepG2 but not HT-29 cells. Analysis of the 24 h-incubation media of HT-29 cells showed that both toxins were completely conjugated, whereas 75% were still present as unconjugated compounds in the 24 h-media of HepG2 cells. Lysates of both cell types fortified with UDPGA were found to convert both toxins into two glucuronides each, but HT-29 cells exhibited a much high activity than HepG2 cells and gave rise to a different ratio of glucuronides. It is concluded that glucuronidation eliminates the DNA strandbreaking potential of AOH and AME, and that the two glucuronides of eachAlternaria toxin are generated by different UGT isoforms.


Alternaria toxins alternariol alternariol methyl ether DNA strand breaks glucuronides 


  1. 1.
    Chelkowski J, Visconti A (eds) (1992)Alternaria. Biology, Plant Diseases and Metabolites. Elsevier, Amsterdam.Google Scholar
  2. 2.
    Scott PM (2001) Analysis of agricultural commodities and foods forAlternaria mycotoxins. J AOAC International 84: 1809–1817Google Scholar
  3. 3.
    Scott PM, Lawrence GA, Lau BPY (2006) Analysis of wines, grape juices and cranberry juices forAlternaria toxins. Mycotoxin Research 22: 142–147CrossRefGoogle Scholar
  4. 4.
    Liu GT, Qian YZ, Zhang P, Dong WH, Qi YM, Guo HT (1992) Etiological role ofAlternaria alternala in human esophageal cancer. Chinese MedJ 105: 394–400Google Scholar
  5. 5.
    Lehmann L, Wagner J, Metzler M (2006) Estrogenic and clastogenic potential of the mycotoxin alternariol in cultured mammalian cells. Food Chem Toxicol 44: 398–408PubMedCrossRefGoogle Scholar
  6. 6.
    Brugger EM, Wagner J, Schumacher DM, Koch K, Podlech J, Metzler M, Lehmann L (2006) Mutagenicity of the mycotoxin alternariol in cultured mammalian cells. Toxicol Lett 164: 221–230PubMedCrossRefGoogle Scholar
  7. 7.
    Fehr M, Pahlke G, Fritz J, Marko D (2007) Alternariol acts as a topoisomerase poison. 29th Mycotoxin Workshop, Fellbach, Germany. Abstract Book p 123Google Scholar
  8. 8.
    Koch K, Podlech J, Pfeiffer E, Metzler M (2005) Total synthesis of alternariol. J Org Chem 70: 3275–3276PubMedCrossRefGoogle Scholar
  9. 9.
    Pfeiffer E, Hoehle SI, Walch SG, Riess A, Sólyom AM, Metzler M (2007) Curcuminoids form reactive glucuronides in vitro. J Agric Food Chem 55: 538–544PubMedCrossRefGoogle Scholar
  10. 10.
    Hartwig A, Dally H, Schlepegrell R (1996) Sensitive analysis of oxidative DNA damage in mammalian cells: use of the bacterial Fpg protein in combination with alkaline unwinding. Toxicol Lett 88: 85–90PubMedCrossRefGoogle Scholar
  11. 11.
    Doehmer J (1993) V79 Chinese hamster cells genetically engineered for cytochrome P450 and their use in mutagenicity and metabolism studies. Toxicology 82: 105–118PubMedCrossRefGoogle Scholar
  12. 12.
    Wooster R, Ebner T, Sutherland L, Clarke D, Burchell B (1993) Drug and xenobiotic glucuronidation catalzed by cloned human liver UDP-glucuronosyltransferases stably expressed in tissue culture cell lines. Toxicology 82:119–129PubMedCrossRefGoogle Scholar
  13. 13.
    Caron P, Trottier J, Verreault M, Bélanger J, Kaeding J, Barbier B (2006) Enzymatic produc tion of bile acid glucuronides used as analytical standards for liquid chromatography-mass spectrometry analysis. Mol Pharm 3: 293–302PubMedCrossRefGoogle Scholar
  14. 14.
    Jansen GH, Nielen MW, Müller M, Hollinan PC, Keijer J (2005) Uptake and metabolism of enterolactone and enterodiol by human colon epithelial cells. Arch Biochem Biophys 435: 74–82PubMedCrossRefGoogle Scholar
  15. 15.
    Olsen M, Visconti A (1988) Metabolism of alteraariol monomethyl ether by porcine liver and intestinal mucosain vitro. Toxicol in Vitro 2: 27–29CrossRefGoogle Scholar
  16. 16.
    Basu NK, Kole L, Kubota S, Owens IS (2004) Human UDP-glucuronosyltransferases show atypical metabolism of mycophenolic acid and inhibition by curcumin. Drag Metab Dispos 32: 768–773CrossRefGoogle Scholar

Copyright information

© Society of Mycotoxin Research and Springer 2007

Authors and Affiliations

  1. 1.Institute of Applied Biosciences, Chair of Food ChemistryUniversity of KarlsruheKarlsruheGermany

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