LAUSR

Co-occurrence of aflatoxin B1 (AFB1) and deoxynivalenol (DON) is one of the most common mycotoxin contaminations in cereal crops and food ingredients. However, the mechanism of their combined toxicity is poorly understood. In the current investigation, the hepatoma HepG2/C3A cell line was used to explore the combined cytotoxicity of AFB1 and DON. The values of IC50, based on a sulforhodamine B (SRB) assay, were 4.5 mM and 18.7 mM for DON and AFB1, respectively. The analysis of cytotoxicity endpoints using the combination index (CI) theory revealed that the changes of mitochondrial membrane permeability and ATP resulted from an additive cytotoxic effect (CI≈1) of AFB1 and DON. However, the endpoints of double strand DNA (ds-DNA), reactive oxygen species (ROS) and cell viability (SRB) were synergistically (CI<1) affected in a dose-dependent manner. RNA-seq analysis demonstrated a number of uniquely expressed genes in their combination (AFB1: 2.5 mM, DON: 0.56 mM), indicating a synergistic interaction betwee...