title: Low doses of ochratoxin A induce micronucleus formation and delay  DNA repair in human lymphocytes.
abstract: The contamination of food commodities by fungal toxins has attracted great interest because many of these mycotoxins are responsible for different diseases, including cancer and other chronic illnesses. Ochratoxin A (OTA) is a mycotoxin naturally present in food, and long-term exposure to food contaminated with low levels of OTA has been associated with renal cancer. In the present study, the cytotoxicity, cytostaticity, and genotoxicity of OTA (0.075-15 µM) in human lymphocytes were evaluated. A comet assay, a modified comet assay (DNA repair assay), which uses N-hydroxyurea (NHU) to detect non-repaired lesions produced by OTA, and a cytokinesis-blocked micronucleus assay were used. Treatments with OTA were not cytotoxic, but OTA caused a cytostatic effect in human lymphocytes at a concentration of 15 µM. OTA (0.075-5 µM) produced a slight increase in the percentage of DNA in the comets and a delay in the DNA repair capacity of the lymphocytes. Micronucleus (MN) induction was observed at OTA concentrations of 1.5 and 5 µM. Our results indicate that OTA induces DNA stable damage at low doses that are neither cytotoxic nor cytostatic, and OTA delays the DNA repair kinetics. These findings indicate that OTA affects two pivotal events in the carcinogenesis pathway.
authors.affiliation: Food Technology Department, Lleida University, UTPV-XaRTA, Agrotecnio Center, Av. Rovira Roure 191, Lleida, 25198, Spain.
authors.forename: Cyndia A
authors.initials: CA
authors.lastname: González-Arias
authors.forename: Alma B
authors.initials: AB
authors.lastname: Benitez-Trinidad
authors.forename: Monserrat
authors.initials: M
authors.lastname: Sordo
authors.forename: Lourdes
authors.initials: L
authors.lastname: Robledo-Marenco
authors.forename: Irma M
authors.initials: IM
authors.lastname: Medina-Díaz
authors.forename: Briscia S
authors.initials: BS
authors.lastname: Barrón-Vivanco
authors.forename: Sonia
authors.initials: S
authors.lastname: Marín
authors.forename: Vicente
authors.initials: V
authors.lastname: Sanchis
authors.forename: Antonio J
authors.initials: AJ
authors.lastname: Ramos
authors.forename: Aurora E
authors.initials: AE
authors.lastname: Rojas-García
mesh_terms: D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D020552:Comet Assay; D048749:Cytokinesis / Q000187:drug effects; D004249:DNA Damage; D004260:DNA Repair / Q000187:drug effects*; D006801:Humans; D008214:Lymphocytes / Q000187:drug effects*; D008297:Male; D015162:Micronucleus Tests; D009153:Mutagens / Q000633:toxicity*; D009793:Ochratoxins / Q000633:toxicity*; D055815:Young Adult
chemical_list: D009153:Mutagens; D009793:Ochratoxins; C025589:ochratoxin A