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The aflatoxin B1-fumonisin B1 toxicity in BRL-3A hepatocytes is associated to induction of cytochrome P450 activity and arachidonic acid metabolism.
- Source :
- Environmental Toxicology; Jun2017, Vol. 32 Issue 6, p1711-1724, 14p
- Publication Year :
- 2017
-
Abstract
- Human oral exposure to aflatoxin B<subscript>1</subscript> (AFB<subscript>1</subscript>) and fumonisin B<subscript>1</subscript> (FB<subscript>1</subscript>) is associated with increased hepatocellular carcinoma. Although evidence suggested interactive AFB<subscript>1</subscript>-FB<subscript>1</subscript> hepatotoxicity, the underlying mechanisms remain mostly unidentified. This work was aimed at evaluating the possible AFB<subscript>1</subscript>-FB<subscript>1</subscript> interplay to induce genetic and cell cycle toxicities in BRL-3A rat hepatocytes, reactive oxygen species (ROS) involvement, and the AFB<subscript>1</subscript> metabolizing pathways cytochrome P450 (CYP) and arachidonic acid (ArAc) metabolism as ROS contributors. Flow cytometry of stained BRL-3A hepatocytes was used to study the cell cycle (propidium iodide), ROS intracellular production (DCFH-DA, HE, DAF-2 DA), and phospholipase A activity (staining with bis-BODIPY FL C11-PC). The CYP1A activity was assessed by the 7-ethoxyresorufin-O-deethylase (EROD) assay. Despite a 48-h exposure to FB<subscript>1</subscript> (30 μM) not being genotoxic, the AFB<subscript>1</subscript> (20 μM)-induced micronucleus frequency was overcome by the AFB<subscript>1</subscript>-FB<subscript>1</subscript> mixture (MIX), presumably showing toxin interaction. The mycotoxins blocked G1/S-phase, but only MIX caused cell death. Overall, the oxidative stress led these alterations as the pretreatment with N-acetyl-l-cysteine reduced such toxic effects. While AFB<subscript>1</subscript> had a major input to the MIX pro-oxidant activity, with CYP and ArAc metabolism being ROS contributors, these pathways were not involved in the FB<subscript>1</subscript>-elicited weak oxidative stress. The MIX-induced micronucleus frequency in N-acetyl- l-cysteine pretreated cells was greater than that caused by AFB<subscript>1</subscript> without antioxidants, suggesting enhanced AFB<subscript>1</subscript> direct genotoxicity probably owing to the higher CYP activity and ArAc metabolism found in MIX. The metabolic pathways modulation by AFB<subscript>1</subscript>-FB<subscript>1</subscript> mixtures could raise its hepatocarcinogenic properties. [ABSTRACT FROM AUTHOR]
- Subjects :
- AFLATOXINS
LIVER cells
CYTOCHROMES
ARACHIDONIC acid
FUMONISINS
Subjects
Details
- Language :
- English
- ISSN :
- 15204081
- Volume :
- 32
- Issue :
- 6
- Database :
- Complementary Index
- Journal :
- Environmental Toxicology
- Publication Type :
- Academic Journal
- Accession number :
- 122961034
- Full Text :
- https://doi.org/10.1002/tox.22395