title: Ochratoxin A at low concentrations inhibits in vitro growth of canine umbilical cord matrix mesenchymal stem cells through oxidative chromatin and DNA damage.
abstract: Ochratoxin A (OTA) exposure during pregnancy in laboratory animals induces delayed/abnormal embryo development. Foetal adnexa-derived mesenchymal stem cells (MSCs) could help evaluate the developmental risk of exposure to chemicals in advanced gestational age. We tested the effects of OTA at concentrations ranging from 2.5×10(-4) to 25nM on growth parameters of canine umbilical cord matrix (UCM)-derived MSCs. The hypothesis that oxidative chromatin and DNA damage could underlie OTA-mediated cell toxicity was also investigated. After in vitro exposure, OTA significantly decreased cell density and increased doubling time in a passage- and concentration-dependent manner and no exposed cells survived beyond passage 5. Significantly higher rates of cells showed condensed and fragmented chromatin and oxidized DNA, as assessed by OxyDNA assay. These findings showed that in vitro exposure to OTA, at picomolar levels, perturbs UCM-MSC growth parameters through oxidative chromatin and DNA damage, suggesting possible consequences on canine foetal development.
authors.affiliation: Veterinary Clinics and Animal Production Section, Department of Emergency and Organ Transplantations (DETO), University of Bari Aldo Moro, Str. Prov. Casamassima km 3, 70010 Valenzano (BA), Italy. Electronic address: lucia.rutigliano1@gmail.com.
authors.forename: Lucia
authors.initials: L
authors.lastname: Rutigliano
authors.affiliation: Veterinary Clinics and Animal Production Section, Department of Emergency and Organ Transplantations (DETO), University of Bari Aldo Moro, Str. Prov. Casamassima km 3, 70010 Valenzano (BA), Italy. Electronic address: luisa.valentini@uniba.it.
authors.forename: Luisa
authors.initials: L
authors.lastname: Valentini
authors.affiliation: Istituto Zooprofilattico Sperimentale Puglia e Basilicata, Via Manfredonia 20, 71121 Foggia, Italy; Dipartimento di Bioscienze, Biotecnologie e Biofarmaceutica (DBBB), Università degli Studi di Bari Aldo Moro, Str. Prov. Casamassima Km 3, 70010 Valenzano (BA), Italy. Electronic address: nicmartino@libero.it.
authors.forename: Nicola Antonio
authors.initials: NA
authors.lastname: Martino
authors.affiliation: Istituto di Biologia e Biotecnologia Agraria (IBBA) Consiglio Nazionale delle Ricerche (CNR), Unità Org. di Supporto di Lodi-c/o Parco Tecnologico Padano, via Einstein, 26500 Lodi, Italy. Electronic address: flavia.pizzi@ibba.cnr.it.
authors.forename: Flavia
authors.initials: F
authors.lastname: Pizzi
authors.affiliation: Department of Veterinary Sciences, University of Messina, Polo Universitario SS Annunziata, 98168 Messina, Italy. Electronic address: zanghia@unime.it.
authors.forename: Antonina
authors.initials: A
authors.lastname: Zanghì
authors.affiliation: Dipartimento di Bioscienze, Biotecnologie e Biofarmaceutica (DBBB), Università degli Studi di Bari Aldo Moro, Str. Prov. Casamassima Km 3, 70010 Valenzano (BA), Italy. Electronic address: mariaelena.dellaquila@uniba.it.
authors.forename: Maria Elena
authors.initials: ME
authors.lastname: Dell'Aquila
authors.affiliation: Institute of Sciences of Food Production (ISPA), National Research Council of Italy (CNR), Via G. Amendola 122/O, 70125 Bari, Italy. Electronic address: fiorenza.minervini@ispa.cnr.it.
authors.forename: Fiorenza
authors.initials: F
authors.lastname: Minervini
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D002843:Chromatin / Q000378:metabolism*; D004249:DNA Damage; D004285:Dogs; D005260:Female; D059630:Mesenchymal Stem Cells / Q000187:drug effects* / Q000378:metabolism; D009793:Ochratoxins / Q000633:toxicity*; D010084:Oxidation-Reduction; D011247:Pregnancy; D014470:Umbilical Cord / Q000166:cytology
chemical_list: D002843:Chromatin; D009793:Ochratoxins; C025589:ochratoxin A
keywords: Apoptosis; Dog; Ochratoxin A; Oxidative DNA damage; Umbilical cord matrix mesenchymal stem cells