Multi-Omics Reveal Additive Cytotoxicity Effects of Aflatoxin B1 and Aflatoxin M1 Toward Intestinal NCM460 Cells

Overview

Journal Toxins (Basel)

Publisher MDPI

Specialty Toxicology

Date 2022 Jun 23

PMID 35737029

Authors

Ya-Nan Gao

Xue Yang

Jia-Qi Wang

Hui-Min Liu

Nan Zheng

Affiliations

Soon will be listed here.

Abstract

Aflatoxin B1 (AFB1) is a common crop contaminant, while aflatoxin M1 (AFM1) is implicated in milk safety. Humans are likely to be simultaneously exposed to AFB1 and AFM1; however, studies on the combined interactive effects of AFB1 and AFM1 are lacking. To fill this knowledge gap, transcriptomic, proteomic, and microRNA (miRNA)-sequencing approaches were used to investigate the toxic mechanisms underpinning combined AFB1 and AFM1 actions in vitro. Exposure to AFB1 (1.25-20 μM) and AFM1 (5-20 μM) for 48 h significantly decreased cell viability in the intestinal cell line, NCM460. Multi-omics analyses demonstrated that additive toxic effects were induced by combined AFB1 (2.5 μM) and AFM1 (2.5 μM) in NCM460 cells and were associated with p53 signaling pathway, a common pathway enriched by differentially expressed mRNAs/proteins/miRNAs. Specifically, based on p53 signaling, cross-omics showed that AFB1 and AFM1 reduced NCM460 cell viability via the hsa-miR-628-3p- and hsa-miR-217-5p-mediated regulation of cell surface death receptor (FAS), and also the hsa-miR-11-y-mediated regulation of cyclin dependent kinase 2 (CDK2). We provide new insights on biomarkers which reflect the cytotoxic effects of combined AFB1 and AFM1 toxicity.

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