Ochratoxin A induces global DNA hypomethylation and oxidative stress in neuronal cells in vitro
| Autor: | Helga Stopper, Lusine Khondkaryan, Nelly Babayan, Ruzanna Grigoryan, Gohar Tadevosyan, Natalya Sarkisyan, Rouben Haroutiounian |
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| Rok vydání: | 2019 |
| Předmět: |
Toxicology
medicine.disease_cause 01 natural sciences Microbiology Chromosomes Cell Line 03 medical and health sciences Mice medicine Animals Humans Epigenetics Neurons 0303 health sciences Chemistry 030302 biochemistry & molecular biology 010401 analytical chemistry Neurotoxicity DNA Methylation Mycotoxins medicine.disease Molecular biology Ochratoxins In vitro 0104 chemical sciences Oxidative Stress Cell culture Toxicity Neurotoxicity Syndromes Reactive Oxygen Species Oxidative stress Genotoxicity Biotechnology DNA hypomethylation |
| Zdroj: | Mycotoxin research. 36(1) |
| ISSN: | 1867-1632 |
| Popis: | Recently, it was reported that ochratoxin A (OTA) mycotoxin, produced by a number of Aspergillus and Penicillium fungal species, may cause neuropsychological impairment or mental and emotional disorders but the mechanism of neurotoxicity remains unknown. Adverse effects of OTA in human (SHSY5Y) and mouse (HT22) neuronal cell lines were studied in vitro. OTA was found to be non-cytotoxic in both cell lines at concentrations 2.5–30 μmol/l, which are above the levels reported for human and animal plasma. OTA led to slightly elevated chromosomal instability in HT22 cells at concentrations of 15–30 μmol/l after 48 h, while in SHSY5Y cells, no evidence for genotoxic effects was observed at concentrations of 2.5–30 μmol/l. OTA treatment at 10 μmol/l resulted in elevated levels of unmethylated cytosines in CpG dinucleotides (up to 1.4-fold), elevated levels of intracellular reactive oxygen species (up to 1.6-fold), and in elevated levels of oxidized DNA purines (up to 2.2-fold) in both cell lines. Detected global DNA hypomethylation and oxidative stress were found to be reversible in 96 h and 24–72 h, respectively. In general, the observed pattern of OTA-induced effects in both cell lines was similar, but HT22 cells exhibited higher sensitivity, as well as better repair capacity in response to OTA toxicity. In conclusion, the results suggest that oxidative stress and epigenetic changes are directly involved in OTA-induced neurotoxicity, while cytotoxicity and genotoxicity cannot be considered as primary cause of toxicity in neuronal cells in vitro. |
| Databáze: | OpenAIRE |
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