title: Patulin transformation products and last intermediates in its biosynthetic pathway, E- and Z-ascladiol, are not toxic to human cells.
abstract: 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.
authors.affiliation: Toxalim (Research Centre in Food Toxicology), INRA, ENVT, INP-Purpan, UPS, Université de Toulouse, Toulouse, France.|ENVT, INP, UMR 1331, Toxalim, Université de Toulouse III, 31076, Toulouse, France.|Centre d'Analyses et de Recherches (Faculté des Sciences), Université Saint-Joseph, Campus des Sciences et Technologies, Mar Roukos, Mkallès, Riad El Solh, P.O. Box 11-514, Beirut, 1107 2050, Lebanon.
authors.forename: Joanna
authors.initials: J
authors.lastname: Tannous
authors.affiliation: Toxalim (Research Centre in Food Toxicology), INRA, ENVT, INP-Purpan, UPS, Université de Toulouse, Toulouse, France.|ENVT, INP, UMR 1331, Toxalim, Université de Toulouse III, 31076, Toulouse, France.
authors.forename: Selma P
authors.initials: SP
authors.lastname: Snini
authors.affiliation: Toxalim (Research Centre in Food Toxicology), INRA, ENVT, INP-Purpan, UPS, Université de Toulouse, Toulouse, France.|ENVT, INP, UMR 1331, Toxalim, Université de Toulouse III, 31076, Toulouse, France.|Centre d'Analyses et de Recherches (Faculté des Sciences), Université Saint-Joseph, Campus des Sciences et Technologies, Mar Roukos, Mkallès, Riad El Solh, P.O. Box 11-514, Beirut, 1107 2050, Lebanon.
authors.forename: Rhoda
authors.initials: R
authors.lastname: El Khoury
authors.affiliation: Toxalim (Research Centre in Food Toxicology), INRA, ENVT, INP-Purpan, UPS, Université de Toulouse, Toulouse, France.|ENVT, INP, UMR 1331, Toxalim, Université de Toulouse III, 31076, Toulouse, France.
authors.forename: Cécile
authors.initials: C
authors.lastname: Canlet
authors.affiliation: Toxalim (Research Centre in Food Toxicology), INRA, ENVT, INP-Purpan, UPS, Université de Toulouse, Toulouse, France.|ENVT, INP, UMR 1331, Toxalim, Université de Toulouse III, 31076, Toulouse, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Pinton
authors.affiliation: Toxalim (Research Centre in Food Toxicology), INRA, ENVT, INP-Purpan, UPS, Université de Toulouse, Toulouse, France.|ENVT, INP, UMR 1331, Toxalim, Université de Toulouse III, 31076, Toulouse, France.
authors.forename: Yannick
authors.initials: Y
authors.lastname: Lippi
authors.affiliation: Toxalim (Research Centre in Food Toxicology), INRA, ENVT, INP-Purpan, UPS, Université de Toulouse, Toulouse, France.|ENVT, INP, UMR 1331, Toxalim, Université de Toulouse III, 31076, Toulouse, France.
authors.forename: Imourana
authors.initials: I
authors.lastname: Alassane-Kpembi
authors.affiliation: Toxalim (Research Centre in Food Toxicology), INRA, ENVT, INP-Purpan, UPS, Université de Toulouse, Toulouse, France.|ENVT, INP, UMR 1331, Toxalim, Université de Toulouse III, 31076, Toulouse, France.
authors.forename: Thierry
authors.initials: T
authors.lastname: Gauthier
authors.affiliation: Centre d'Analyses et de Recherches (Faculté des Sciences), Université Saint-Joseph, Campus des Sciences et Technologies, Mar Roukos, Mkallès, Riad El Solh, P.O. Box 11-514, Beirut, 1107 2050, Lebanon.
authors.forename: André
authors.initials: A
authors.lastname: El Khoury
authors.affiliation: Laboratory of Microorganisms and Food Irradiation, Lebanese Atomic Energy Commission-CNRS, Riad El Solh, P.O. Box 11-8281, Beirut, 1107 2260, Lebanon.|Laboratory of Microbiology, Department of Biology, Faculty of Sciences, Lebanese University, Hadath Campus, Beirut, Lebanon.
authors.forename: Ali
authors.initials: A
authors.lastname: Atoui
authors.affiliation: Guelph Research and Development Center, Agriculture and Agri-Food Canada, 93 Stone Road West, Guelph, ON, Canada.
authors.forename: Ting
authors.initials: T
authors.lastname: Zhou
authors.affiliation: Centre d'Analyses et de Recherches (Faculté des Sciences), Université Saint-Joseph, Campus des Sciences et Technologies, Mar Roukos, Mkallès, Riad El Solh, P.O. Box 11-514, Beirut, 1107 2050, Lebanon.
authors.forename: Roger
authors.initials: R
authors.lastname: Lteif
authors.affiliation: Toxalim (Research Centre in Food Toxicology), INRA, ENVT, INP-Purpan, UPS, Université de Toulouse, Toulouse, France.|ENVT, INP, UMR 1331, Toxalim, Université de Toulouse III, 31076, Toulouse, France.
authors.forename: Isabelle P
authors.initials: IP
authors.lastname: Oswald
authors.affiliation: Toxalim (Research Centre in Food Toxicology), INRA, ENVT, INP-Purpan, UPS, Université de Toulouse, Toulouse, France. opuel@toulouse.inra.fr.|ENVT, INP, UMR 1331, Toxalim, Université de Toulouse III, 31076, Toulouse, France. opuel@toulouse.inra.fr.|INRA, UMR 1331 TOXALIM, 180, Chemin de Tournefeuille, 31027, Toulouse, France. opuel@toulouse.inra.fr.
authors.forename: Olivier
authors.initials: O
authors.lastname: Puel
mesh_terms: D018938:Caco-2 Cells; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005663:Furans / Q000378:metabolism / Q000633:toxicity*; D017353:Gene Deletion; D005800:Genes, Fungal; D057809:HEK293 Cells; D018922:HL-60 Cells; D056945:Hep G2 Cells; D006801:Humans; D007536:Isomerism; D009928:Organ Specificity; D010365:Patulin / Q000096:biosynthesis* / Q000633:toxicity*; D010407:Penicillium / Q000235:genetics / Q000378:metabolism
chemical_list: D005663:Furans; C038422:ascladiol; D010365:Patulin
keywords: Ascladiol; Cytotoxicity; Microarray analysis; Patulin synthase; Penicillium expansum; patE gene