Are Aflatoxin precursors of concern for human health? – Precursors

Aflatoxin B1 (AFB1) is a food contaminant known to be the most potent natural carcinogen. The mode of action of this mycotoxin depends on its dihydrobisfuran structure, which makes it mutagenic and genotoxic. Other precursors of the synthesis of AFB1 such as versicolorin A (VerA) are also genotoxic bisfuranoid mycotoxins. However, recent studies suggest that VerA has more complex toxicity than AFB1, encompassing both direct/indirect DNA damage, as well as the disruption of topoisomerases activity, RNA processing, and DNA transcription. Of note, natural compounds disrupting DNA replication/transcription are rare and extremely toxic, but also bear a high therapeutic potential as anti-cancer or anti-viral drugs. Moreover, VerA anthraquinone structure is linked with mitochondrial toxicity, and preliminary data link this mitotoxicity with changes in epigenetics, protein synthesis, and immunity. Other AFB1 precursors show structural similarities with VerA, like the bisfuranoid sterigmatocystin and the anthraquinones Versicolorin B and averufin thus sharing some aspects of VerA toxicity. All these toxins are potentially found co-contaminating food and thus a complex co-exposure is expected. In this project, we propose to provide a complete evaluation of the extent and the mechanisms by which structurally-related AFB1 precursors affect nuclear and mitochondrial DNA integrity, DNA/RNA biology, topoisomerase activity, mitochondrial function, and epigenetic signaling. The co-occurrence of these toxins in foods will be evaluated and their interaction will be evaluated using relevant toxic endpoints based on their individual toxicity. Our results will provide useful data to define the risk associated with exposure to the relatively unknown but potentially dangerous AFB1 precursors.