Díez-Quijada, LeticiaMedrano-Padial, ConcepciónLlana-Ruiz-Cabello, MaríaCatunescu, Giorgiana M.Moyano, RosarioRisalde, Maria A.Cameán, Ana M.Jos, Ángeles2022-07-052022-07-052020-05-26Díez-Quijada L, Medrano-Padial C, Llana-Ruiz-Cabello M, Cătunescu GM, Moyano R, Risalde MA, et al. Cylindrospermopsin-Microcystin-LR Combinations May Induce Genotoxic and Histopathological Damage in Rats. Toxins. 2020 May 26;12(6):348http://hdl.handle.net/10668/3743Cylindrospermopsin (CYN) and microcystins (MC) are cyanotoxins that can occur simultaneously in contaminated water and food. CYN/MC-LR mixtures previously investigated in vitro showed an induction of micronucleus (MN) formation only in the presence of the metabolic fraction S9. When this is the case, the European Food Safety Authority recommends a follow up to in vivo testing. Thus, rats were orally exposed to 7.5 + 75, 23.7 + 237, and 75 + 750 μg CYN/MC-LR/kg body weight (b.w.). The MN test in bone marrow was performed, and the standard and modified comet assays were carried out to measure DNA strand breaks or oxidative DNA damage in stomach, liver, and blood cells. The results revealed an increase in MN formation in bone marrow, at all the assayed doses. However, no DNA strand breaks nor oxidative DNA damage were induced, as shown in the comet assays. The histopathological study indicated alterations only in the highest dose group. Liver was the target organ showing fatty degeneration and necrotic hepatocytes in centrilobular areas, as well as a light mononuclear inflammatory periportal infiltrate. Additionally, the stomach had flaking epithelium and mild necrosis of epithelial cells. Therefore, the combined exposure to cyanotoxins may induce genotoxic and histopathological damage in vivo.enAtribución 4.0 Internacionalhttp://creativecommons.org/licenses/by/4.0/In vivoGenotoxicityCylindrospermopsinMicrocystin-LRMicronucleusComet assayEnzyme-modified comet assayRatsGenotoxicidadCianotoxinasPruebas de micronúcleosEnsayo cometaRatasMedical Subject Headings::Chemicals and Drugs::Heterocyclic Compounds::AlkaloidsMedical Subject Headings::Organisms::Eukaryota::AnimalsMedical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Chemistry Techniques, Analytical::Electrophoresis::Electrophoresis, Agar Gel::Comet AssayMedical Subject Headings::Diseases::Digestive System Diseases::Liver Diseases::Fatty LiverMedical Subject Headings::Check Tags::FemaleMedical Subject Headings::Anatomy::Digestive System::Gastrointestinal Tract::Upper Gastrointestinal Tract::Stomach::Gastric MucosaMedical Subject Headings::Anatomy::Cells::Epithelial Cells::HepatocytesMedical Subject Headings::Check Tags::MaleMedical Subject Headings::Chemicals and Drugs::Biological Factors::Toxins, Biological::Marine ToxinsMedical Subject Headings::Chemicals and Drugs::Polycyclic Compounds::Macrocyclic Compounds::Peptides, Cyclic::MicrocystinsMedical Subject Headings::Anatomy::Cells::Cellular Structures::Intracellular Space::Cell Nucleus::Micronuclei, Chromosome-DefectiveMedical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Genetic Techniques::Mutagenicity Tests::Micronucleus TestsMedical Subject Headings::Phenomena and Processes::Cell Physiological Phenomena::Cell Physiological Processes::Cell Death::NecrosisMedical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Rodentia::Muridae::Murinae::Rats::Rats, Wistarresearch article32466519open access10.3390/toxins120603482072-6651PMC7354441