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dc.contributor.author
Mary, Verónica Sofía
dc.contributor.author
Arias, Silvina Lorena
dc.contributor.author
Otaiza González, Santiago Nicolás
dc.contributor.author
Velez, Pilar Andrea
dc.contributor.author
Rubinstein, Héctor Ramón
dc.contributor.author
Theumer, Martín Gustavo
dc.date.available
2018-06-15T15:13:23Z
dc.date.issued
2017-06
dc.identifier.citation
Mary, Verónica Sofía; Arias, Silvina Lorena; Otaiza González, Santiago Nicolás; Velez, Pilar Andrea; Rubinstein, Héctor Ramón; et al.; The aflatoxin B1-fumonisin B1 toxicity in BRL-3A hepatocytes is associated to induction of cytochrome P450 activity and arachidonic acid metabolism; John Wiley & Sons Inc; Environmental Toxicology; 32; 6; 6-2017; 1711-1724
dc.identifier.issn
1520-4081
dc.identifier.uri
http://hdl.handle.net/11336/48782
dc.description.abstract
Human oral exposure to aflatoxin B1 (AFB1) and fumonisin B1 (FB1) is associated with increased hepatocellular carcinoma. Although evidence suggested interactive AFB1–FB1 hepatotoxicity, the underlying mechanisms remain mostly unidentified. This work was aimed at evaluating the possible AFB1–FB1 interplay to induce genetic and cell cycle toxicities in BRL-3A rat hepatocytes, reactive oxygen species (ROS) involvement, and the AFB1 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 FB1 (30 μM) not being genotoxic, the AFB1 (20 μM)-induced micronucleus frequency was overcome by the AFB1–FB1 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 AFB1 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 FB1-elicited weak oxidative stress. The MIX-induced micronucleus frequency in N-acetyl-l-cysteine pretreated cells was greater than that caused by AFB1 without antioxidants, suggesting enhanced AFB1 direct genotoxicity probably owing to the higher CYP activity and ArAc metabolism found in MIX. The metabolic pathways modulation by AFB1–FB1 mixtures could raise its hepatocarcinogenic properties.
dc.format
application/pdf
dc.language.iso
eng
dc.publisher
John Wiley & Sons Inc
dc.rights
info:eu-repo/semantics/openAccess
dc.rights.uri
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.subject
Cyp1a
dc.subject
Genotoxicity
dc.subject
Mycotoxin Mixture
dc.subject
Oxidative Stress
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Phospholipase A
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Otras Ciencias Biológicas
dc.subject.classification
Ciencias Biológicas
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CIENCIAS NATURALES Y EXACTAS
dc.title
The aflatoxin B1-fumonisin B1 toxicity in BRL-3A hepatocytes is associated to induction of cytochrome P450 activity and arachidonic acid metabolism
dc.type
info:eu-repo/semantics/article
dc.type
info:ar-repo/semantics/artículo
dc.type
info:eu-repo/semantics/publishedVersion
dc.date.updated
2018-06-11T12:58:07Z
dc.identifier.eissn
1522-7278
dc.journal.volume
32
dc.journal.number
6
dc.journal.pagination
1711-1724
dc.journal.pais
Estados Unidos
dc.description.fil
Fil: Mary, Verónica Sofía. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina
dc.description.fil
Fil: Arias, Silvina Lorena. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina
dc.description.fil
Fil: Otaiza González, Santiago Nicolás. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina
dc.description.fil
Fil: Velez, Pilar Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina
dc.description.fil
Fil: Rubinstein, Héctor Ramón. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina
dc.description.fil
Fil: Theumer, Martín Gustavo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina
dc.journal.title
Environmental Toxicology
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/https://onlinelibrary.wiley.com/doi/abs/10.1002/tox.22395
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.1002/tox.22395
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