Journal Article

Patulin transformation products and last intermediates in its biosynthetic pathway, E- and Z-ascladiol, are not toxic to human cells

Oswald, Isabelle, Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098) (RIGHT), El Khoury, André, Transcriptomic impact of Xenobiotics (E23 TRiX), Canlet, Cécile, Zhou, Ting, Lteif, Roger, Atoui, Ali, Agriculture and Agri-Food (AAFC), Partenaires INRAE, Laboratoire d'Excellence : Lipoprotéines et Santé : prévention et Traitement des maladies Inflammatoires et du Cancer (LabEx LipSTIC), Génopole Toulouse Midi-Pyrénées (GENOTOUL), Alassane-Kpembi, Imourana, Snini, Selma, MetaToul AXIOM (E20), EFS-Etablissement français du sang (EFS BFC), Etablissement Français du Sang de Bourgogne Franche-Comté (site de Chalon-sur-Saône) (EFS BFC (site de Chalon-sur-Saône)), Biosynthèse & Toxicité des Mycotoxines (ToxAlim-BioToMyc), Pinton, Philippe, ANR-11-LABX-0021, Lipstic,Lipoprotéines et santé : prévention et traitement des maladies inflammatoires non vasculaires et du cancer, MetaboHUB-Génopole Toulouse Midi-Pyrénées (GENOTOUL), El Khoury, Rhoda, Puel, Olivier, Tannous, Joanna, ToxAlim (ToxAlim), Lebanese Univ

2017

Overview

Patulin is the main mycotoxin contaminating apples. During the brewing of alcoholic beverages, this mycotoxin is degraded to ascladiol, which is also the last precursor of patulin. The present study aims (1) to characterize the last step of the patulin biosynthetic pathway and (2) to describe the toxicity of ascladiol. A patE deletion mutant was generated in Penicillium expansum . In contrast to the wild strain, this mutant does not produce patulin but accumulates high levels of E-ascladiol with few traces of Z-ascladiol. This confirms that patE encodes the patulin synthase involved in the conversion of E-ascladiol to patulin. After purification, cytotoxicities of patulin and E- and Z-ascladiol were investigated on human cell lines from liver, kidney, intestine, and immune system. Patulin was cytotoxic for these four cell lines in a dose-dependent manner. By contrast, both E- and Z-ascladiol were devoid of cytotoxicity. Microarray analyses on human intestinal cells treated with patulin and E-ascladiol showed that the latter, unlike patulin, did not alter the whole human transcription. These results demonstrate that E- and Z-ascladiol are not toxic and therefore patulin detoxification strategies leading to the accumulation of ascladiol are good approaches to limit the patulin risk.

• Publisher: Springer Verlag,CCSD,Springer Berlin Heidelberg,Springer Nature B.V
• Subject: Alcoholic beverages / Apples / Bacteria / Beverages / Biologics / Biomedical and Life Sciences / Biomedicine / Biosynthesis / Biotechnology / Breweries / Brewing / Caco-2 Cells / Cell lines / Cell Survival - drug effects / Clonal deletion / Contamination / Cytotoxicity / Deletion mutant / Detoxification / DNA microarrays / Dose-Response Relationship, Drug / Environmental Health / Furans - metabolism / Furans - toxicity / Gene Deletion / Genes, Fungal / HEK293 Cells / Hep G2 Cells / Hepatocytes / HL-60 Cells / Humans / Immune system / Intermediates / Intestine / Isomerism / Life Sciences / Liver / Occupational Medicine/Industrial Medicine / Organ Specificity / Patulin / Patulin - biosynthesis / Patulin - toxicity / Penicillium - genetics / Penicillium - metabolism / Pharmacology/Toxicology / Purification / Toxicity / Toxicology / Toxins / Transcription / Vegetal toxicology and mycotoxicology