The aflatoxin B 1 -fumonisin B 1 toxicity in BRL-3A hepatocytes is associated to induction of cytochrome P450 activity and arachidonic acid metabolism

MARY, VERÓNICA S.; ARIAS, SILVINA L.; OTAIZA, SANTIAGO N.; VELEZ, PILAR A.; RUBINSTEIN, HÉCTOR R.; THEUMER, MARTÍN G.

ENVIRONMENTAL TOXICOLOGY

JOHN WILEY & SONS INC

Año: 2017 vol. 32 p. 1711 - 1711

1520-4081

uman 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