Abstract |
The Alternaria mycotoxins alternariol (AOH) and alternariol methyl ether ( AME) are potential carcinogens. As planar compounds, AOH and AME are preferentially metabolized by cytochrome P450 ( CYP) 1A1 and 1A2. The most prominent regulator of CYP1A1 is the dimeric transcription factor complex AhR/ARNT, which is activated by planar ligands. Therefore, we studied the activation of AhR/ARNT by AOH and AME and monitored CYP1A1 induction in murine hepatoma cells (Hepa-1c1c7). Indeed, AOH and AME enhanced the levels of CYP1A1 in Hepa-1c1c7 cells but not in cells with inactivated AhR (Hepa-1c1c12) or ARNT (Hepa-1c1c4). AOH and AME did not increase the production of reactive oxygen species but reduced cell counts in Hepa-1c1c7 cells after 24 and 48 h. This effect, however, was independent of AhR/ARNT. At 48 h, AOH and AME increased apoptosis dependent on AhR and ARNT. In conclusion, AOH and AME are novel inducers of the AhR/ARNT pathway, which mediates induction of CYP1A1 and apoptosis and might thereby contribute to the toxicity of these mycotoxins.
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Authors | Ilona Schreck, Ute Deigendesch, Britta Burkhardt, Doris Marko, Carsten Weiss |
Journal | Archives of toxicology
(Arch Toxicol)
Vol. 86
Issue 4
Pg. 625-32
(Apr 2012)
ISSN: 1432-0738 [Electronic] Germany |
PMID | 22120949
(Publication Type: Journal Article)
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Chemical References |
- Arnt protein, mouse
- Lactones
- Mycotoxins
- Receptors, Aryl Hydrocarbon
- Aryl Hydrocarbon Receptor Nuclear Translocator
- Cytochrome P-450 CYP1A1
- alternariol
- alternariol monomethyl ether
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Topics |
- Animals
- Aryl Hydrocarbon Receptor Nuclear Translocator
(drug effects, metabolism)
- Blotting, Western
- Carcinoma, Hepatocellular
(drug therapy, metabolism, pathology)
- Cell Line, Tumor
- Cell Survival
(drug effects)
- Cytochrome P-450 CYP1A1
(biosynthesis)
- Enzyme Induction
(drug effects)
- Hepatocytes
(drug effects, metabolism, pathology)
- Lactones
(toxicity)
- Mice
- Mycotoxins
(toxicity)
- Receptors, Aryl Hydrocarbon
(drug effects, metabolism)
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