4^th International Food Safety, Quality & Policy Conference

Ochratoxin A (OTA) and citrinin (CTN) are very important mycotoxins and often found in the same food and feed stuff. OTA exposure may lead to genotoxicity and carcinogenicity, while CTN is noticed by its nephrotoxicity. In the present study, individual and combined cytotoxicity of OTA and CTN against HEK293 cells were determined by the MTT assay, which showed a toxicologic synergism caused by the interaction of OTA and CTN. In addition, the results revealed that CTN led to the HEK293 cells accumulated in G2/M stage, and the combined treatment of CTN and OTA led to a dramatic increase in S and G2/M stages, but OTA treatment alone could not induce the cell cycle arrest. Furthermore, the HEK293 cells suffered by individual and combined treatment of OTA and CTN were performed transcriptome and MicroRNA sequencing with illumina Hiseq2500 platform, which indicated 133 miRNAs and 266 target genes were significantly involved. The expressions of certain miRNAs and target genes were also validated by quantitative real-time PCR. The correlations between miRNAs and their target genes associated with apoptotic signaling were furthermore analyzed by pmi-RB-REPORTTM luciferase assay system. This study provided intensive molecular evidences on toxicological basis of OTA and CTN poisoning to human HEK293 cells.