Transcriptomic changes associated to the exposure of intestinal cells to the mycotoxin Versicolorin A

Versicolorin A (VerA), a precursor of the potent carcinogen aflatoxin B1 (AFB1), is an emerging mycotoxin. Recent studies have described the mutagenic and genotoxic ability of VerA, but the mechanisms of its toxicity remain to be discovered. In the present study, we investigated the early (6 h) transcriptomic changes induced by VerA in differentiated intestinal cells at non-cytotoxic conditions (1 and 3 µM) and compared its effects to those of AFB1 at 1µM. Our results showed that VerA, but not AFB1, induced significant changes in global gene expression profiles. Both toxins induced gene expression changes related to known elements of their toxicity, such as mutagenicity, genotoxicity, oxidative stress and apoptosis. However, we also observed novel features of VerA toxicity, including the ability to induce mitochondrial dysfunction, which leads to the induction of a type-1 interferon response mediated by cGAS-STING. VerA also induced changes in the expression of genes involved in the regulation of cell shape and adhesion, transcription/translation as well as genes associated with tumor biology. Our findings provide new evidence of VerA toxicity and highlight the need to further evaluate its hazards and the risk associated with its presence in food. The experimental design included four biological and three technical replicates for each exposure condition. Exposure conditions included 2 toxin concentrations (1 and 3 microMolar) and 2 time-points (6 and 24h). Control samples were included at each time point, corresponding to the vehicle where toxin was diluted (DMSO)