title: Genotoxicity of microcystin-LR in in vitro and in vivo experimental models.
abstract: Microcystin-LR (MCLR) is a cyanobacterial toxin known for its acute hepatotoxicity. Despite being recognized as tumour promoter, its genotoxicity is far from being completely clarified, particularly in organs other than liver. In this work, we used the comet and/or the micronucleus (MN) assays to study the genotoxicity of MCLR in kidney- (Vero-E6) and liver-derived (HepG2) cell lines and in blood cells from MCLR-exposed mice. MCLR treatment (5 and 20 μM) caused a significant induction in the MN frequency in both cell lines and, interestingly, a similar positive effect was observed in mouse reticulocytes (37.5 μg MCLR/kg, i.p. route). Moreover, the FISH-based analysis of the MN content (HepG2 cells) suggested that MCLR induces both chromosome breaks and loss. On the other hand, the comet assay results were negative in Vero-E6 cells and in mouse leukocytes, with the exception of a transient increase in the level of DNA damage 30 minutes after mice exposure. Overall, the present findings contributed to increase the weight of evidence in favour of MCLR genotoxicity, based on its capacity to induce permanent genetic damage either in vitro or in vivo. Moreover, they suggest a clastogenic and aneugenic mode of action that might underlie a carcinogenic effect.
authors: Department of Environmental Health, National Institute of Health Dr. Ricardo Jorge, Avenida Padre Cruz, 1649-016 Lisbon, Portugal.
authors: Elsa
authors: 0000-0002-1797-4456
authors: E
authors: Dias
authors: Department of Human Genetics, National Institute of Health Dr. Ricardo Jorge, Avenida Padre Cruz, 1649-016 Lisbon, Portugal.
authors: Henriqueta
authors: 0000-0001-9744-7332
authors: H
authors: Louro
authors: Department of Human Genetics, National Institute of Health Dr. Ricardo Jorge, Avenida Padre Cruz, 1649-016 Lisbon, Portugal.
authors: Miguel
authors: 0000-0001-6370-3051
authors: M
authors: Pinto
authors: Department of Human Genetics, National Institute of Health Dr. Ricardo Jorge, Avenida Padre Cruz, 1649-016 Lisbon, Portugal.
authors: Telma
authors: T
authors: Santos
authors: Department of Human Genetics, National Institute of Health Dr. Ricardo Jorge, Avenida Padre Cruz, 1649-016 Lisbon, Portugal.
authors: Susana
authors: 0000-0003-4106-6623
authors: S
authors: Antunes
authors: Department of Environmental Health, National Institute of Health Dr. Ricardo Jorge, Avenida Padre Cruz, 1649-016 Lisbon, Portugal.
authors: Paulo
authors: 0000-0003-4819-2112
authors: P
authors: Pereira
authors: Department of Human Genetics, National Institute of Health Dr. Ricardo Jorge, Avenida Padre Cruz, 1649-016 Lisbon, Portugal.
authors: Maria João
authors: MJ
authors: Silva
mesh_terms: D000818:Animals; D001427:Bacterial Toxins / Q000008:administration & dosage*; D002522:Chlorocebus aethiops; D020552:Comet Assay; D000087522:Cyanobacteria Toxins; D056945:Hep G2 Cells / Q000187:drug effects; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D066298:In Vitro Techniques; D007962:Leukocytes / Q000187:drug effects; D008099:Liver / Q000187:drug effects* / Q000473:pathology; D008387:Marine Toxins / Q000008:administration & dosage*; D051379:Mice; D052998:Microcystins / Q000008:administration & dosage* / Q000633:toxicity*; D015162:Micronucleus Tests; D009152:Mutagenicity Tests; D009153:Mutagens / Q000633:toxicity*; D014709:Vero Cells / Q000187:drug effects
chemical_list: D001427:Bacterial Toxins; D000087522:Cyanobacteria Toxins; D008387:Marine Toxins; D052998:Microcystins; D009153:Mutagens; C057862:cyanoginosin LR