title: An in vitro investigation on the cytotoxic and nuclear receptor transcriptional activity of the mycotoxins fumonisin B1 and beauvericin.
abstract: Fumonisin B1 (FB1) and beauvericin (BEA) are secondary metabolites of filamentous fungi, which under appropriate temperature and humidity conditions may develop on various foods and feeds. To date few studies have been performed to evaluate the toxicological and endocrine disrupting effects of FB1 and BEA. The present study makes use of various in vitro bioassays including; oestrogen, androgen, progestagen and glucocorticoid reporter gene assays (RGAs) for the study of nuclear receptor transcriptional activity, the thiazolyl blue tetrazolium bromide (MTT) assay to monitor cytotoxicity and high content analysis (HCA) for the detection of pre-lethal toxicity in the RGA and Caco-2 human colon adenocarcinoma cells. At the receptor level, 0.001-10μM BEA or FB1 did not induce any agonist responses in the RGAs. However at non-cytotoxic concentrations, an antagonistic effect was exhibited by FB1 on the androgen nuclear receptor transcriptional activity at 10μM and BEA on the progestagen and glucocorticoid receptors at 1μM. MTT analysis showed no decrease in cell viability at any concentration of FB1, whereas BEA showed a significant decrease in viability at 10μM. HCA analysis confirmed that the reduction in the progestagen receptor transcriptional activity at 1μM BEA was not due to pre-lethal toxicity. In addition, BEA (10μM) induced significant toxicity in both the TM-Luc (progestagen responsive) and Caco-2 cells.
authors.affiliation: Laboratory of Toxicology, Faculty of Pharmacy, University of Valencia, Av. Vicent Andrés Estellés s/n, 46100 Burjassot, Valencia, Spain.
authors.forename: Celia
authors.initials: C
authors.lastname: Fernández-Blanco
authors.affiliation: Institute for Global Food Security, School of Biological Sciences, Queen's University, Belfast, Northern Ireland, United Kingdom.
authors.forename: Caroline
authors.initials: C
authors.lastname: Frizzell
authors.affiliation: Institute for Global Food Security, School of Biological Sciences, Queen's University, Belfast, Northern Ireland, United Kingdom.
authors.forename: Maeve
authors.initials: M
authors.lastname: Shannon
authors.affiliation: Laboratory of Toxicology, Faculty of Pharmacy, University of Valencia, Av. Vicent Andrés Estellés s/n, 46100 Burjassot, Valencia, Spain.
authors.forename: Maria-Jose
authors.initials: MJ
authors.lastname: Ruiz
authors.affiliation: Institute for Global Food Security, School of Biological Sciences, Queen's University, Belfast, Northern Ireland, United Kingdom. Electronic address: l.connolly@qub.ac.uk.
authors.forename: Lisa
authors.initials: L
authors.lastname: Connolly
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D018938:Caco-2 Cells; D002467:Cell Nucleus / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D002470:Cell Survival / Q000187:drug effects; D003110:Colonic Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D047630:Depsipeptides / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D052244:Endocrine Disruptors / Q000633:toxicity*; D037341:Fumonisins / Q000633:toxicity*; D017930:Genes, Reporter; D006801:Humans; D011944:Receptors, Androgen / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D011965:Receptors, Glucocorticoid / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D011980:Receptors, Progesterone / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects*
chemical_list: C410798:AR protein, human; D047630:Depsipeptides; D052244:Endocrine Disruptors; D037341:Fumonisins; D011944:Receptors, Androgen; D011965:Receptors, Glucocorticoid; D011980:Receptors, Progesterone; C004456:beauvericin; C056933:fumonisin B1
keywords: Beauvericin; Endocrine disruptor; Fumonisin B1; High Content Analysis; Mycotoxin; Reporter gene assay