TITLE

DIMBOA and DIBOA, two naturally occuring benzoxazinoides, cause aneuploidy in a human-derived liver cell line (HepG2)

AUTHOR(S)
Buchmann, Christoph; Nersesyan, Armen; Kopp, Brigitte; Schauberger, Doris; Darroudi, Firouz; Grummt, Tamara; Krupitza, Georg; Schulte-Hermann, Rolf; Knasmüller, Siegfried
PUB. DATE
January 2007
SOURCE
BMC Pharmacology;2007 Supplement 2, Vol. 7, Special section p1
SOURCE TYPE
Academic Journal
DOC. TYPE
Article
ABSTRACT
Introduction Dihydroxy-7-methoxy-1,4-benzoxazin-3-one (DIMBOA) and 2,4-dihydroxy-1,4-benzoxazin-3-one (DIBOA) are naturally occuring benzoxazinoides (BA) and are found in sprouts of Gramineae. We investigated their genotoxic effects in a human-derived liver cell line (HepG2). Methods The Salmonella/microsome assay (Ames test) was used for pre-screening (TA98, TA100 and YG1024; ± S9). Juices of wheat and maize sprouts were also tested. The effects on HepG2 were tested with the single cell gel electrophoresis assay (SCGE), the micronucleus assay (MN) and pancentromeric probes (CP) with fluorescence in situ hybridization (FISH). Results In the Ames test DIBOA was positive. Effects in YG1024 were little higher as in TA98. DIMBOA was positive in TA100 only. Addition of S9 led to higher mutagenic activities. The sprout juices were clearly positive, however not due to the BAs. The SCGE assay was negative, but the MN assay was positive (DIMBOA at >2.5 µM, DIBOA at >5 µM). The CP showed >80% centromere positive (C+) micronuclei. Conclusion The slight differences between YG1024 and TA98 indicate that acetylation plays no role in the activation. The BAs can be classified as weak bacterial mutagens. It is unclear why the sprout juices were positive. Due to the results of the assays with HepG2, we tested for aneuploidic effects. This was confirmed by the CP result. Aneuploidy is thought to be a key event in cancer induction and no other aneugenic plant-derived substances of dietary relevance are known.
ACCESSION #
35702579

 

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