Transcriptome Analysis of Caco-2 Cells upon the Exposure of Mycotoxin Deoxynivalenol and Its Acetylated Derivatives

Abstract

Deoxynivalenol (DON), 3-acetyldeoxynivalenol (3-ADON) and 15-acetyldeoxynivalenol (15-ADON) are type B trichothecenes; one of the major pollutants in food and feed products. Although the toxicity of DON has been well documented, information on the toxicity of its acetylated derivative remains incomplete. To acquire more detailed insight into 3-ADON and 15-ADON, Caco-2 cells under 0.5 µM DON, 3-ADON and 15-ADON treatment for 24 h were subjected to RNA-seq analysis. In the present study, 2656, 3132 and 2425 differentially expressed genes (DEGs) were selected, respectively, and were enriched utilizing the Kyoto Encyclopedia of Genes and Genomes (KEGG) and the Gene Ontology (GO) database. The upregulation of ataxia-telangiectasia mutated kinase (ATM), WEE1 homolog 2 (WEE2) and downregulation of proliferating cell nuclear antigen (PCNA), minichromosome maintenance (MCMs), cyclin dependent kinase (CDKs), and E2Fs indicate that the three toxins induced DNA damage, inhibition of DNA replication and cell cycle arrest in Caco-2 cells. Additionally, the upregulation of sestrin (SENEs) and NEIL1 implied that the reason for DNA damage may be attributable to oxidative stress. Our study provides insight into the toxic mechanism of 3-ADON and 15-ADON.

Updated Review of the Toxicity of Selected Fusarium Toxins and Their Modified Forms

“…One of the theories concerning this issue is a possible increase in toxicity, which can be attributed to esterification at the C-15 position, and its decrease, which can be attributed to acetylation at the C-3 position. To a certain extent, the differences in the results obtained by the authors can be explained by the fact that the correlation between the chemical structure and toxicity is affected by various interactions, which depend on the cell line used [43,83,84]. DON binds to a ribosome through three hydrogen bonds, while its acetylated derivatives form two bonds: one is formed within the epoxy group and the other within the hydroxyl group.…”

“…The available data on the assessment of DON and its modified forms for cytotoxicity are not clear. Depending on the methods applied, cell lines, toxin concentrations, and exposure times, the results obtained varied [25,30,31,39,41,43,82]. Some studies have pointed to higher cytotoxicity of DON compared with that of its acetylated forms.…”

“…However, most publications have demonstrated that 3-AcDON has a relatively low toxicity. The comparison of 15-AcDON cytotoxicity data with those of DON has shown that no statistically significant differences occur between the cytotoxicity of the two compounds [23,25,31,43,82].…”

“…These studies also demonstrated that DON derivatives had stronger toxic effect on proliferative cells. The increased sensitivity of the cells to DON and its derivatives is associated with translation inhibition and a change in the activity of metabolically vital enzymes [25,43]. Moreover, negligible or no DON-3G toxicity has been demonstrated in IPEC-J2, Caco-2, and GES-1 cell lines [31,82,86,87].…”

“…However, these aforementioned methods have significant limitations, as it is not possible to compare the mechanisms associated with toxic effects of parent toxins and those associated with their modified forms. Over the last few years, several studies, which involved molecular biology techniques and in silico analyses, have been aimed at gaining insight into some aspects of toxicity shown by modified Fusarium toxins [32,36,[39][40][41][42][43][44][45][46][47]. Numerous studies, which assessed the cytotoxicity of these compounds by using different cell lines and approaches and evaluated the influence of the interaction between toxins on the intensity of their induced effects, have also been published [32,33,35,39,48].…”