期刊
CHEMOSPHERE
卷 214, 期 -, 页码 623-632出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.chemosphere.2018.09.155
关键词
beta-N-Methylamino-L-alanine; Human blood cells; DNA damage; Non-target cells; Genotoxicity
资金
- Institute for Medical Research and Occupational Health, Croatia
- Slovenian Research Agency [P1-0245]
- Republic of Croatia [BI-HR/14-15-004, BI-HR/18-19-003]
- COST Action [CA15132 (hCOMET), ES1105 (CYANOCOST)]
- Republic of Slovenia [BI-HR/14-15-004, BI-HR/18-19-003]
The non-proteinogenic amino acid beta-N-methylamino-L-alanine (BMAA) is associated with the development of neurodegenerative diseases such as Alzheimer's disease, amyotrophic lateral sclerosis/parkinsonism-dementia complex (ALS-PDC) and amyotrophic lateral sclerosis. BMAA is known to induce neurotoxic effects leading to neurodegeneration via multiple mechanisms including misfolded protein accumulation, glutamate induced excitotoxicity, calcium dyshomeostasis, endoplasmic reticulum stress and oxidative stress. In the present study, for the first time, genotoxic activity of BMAA (2.5, 5, 10 and 20 mu g/mL) was studied in human peripheral blood cells (HPBCs) using the comet and cytokinesis-block micronucleus cytome assays. In addition, the influence of BMAA on the oxidative stress was assessed. At non-cytotoxic concentrations BMAA did not induce formation of DNA strand breaks in HPBCs after 4 and 24 h exposure; however, it significantly increased the number of micronuclei after 24 and 48 hat 20 mu g/mL and nucleoplasmic bridges after 48 hat 20 mu g/mL. The frequency of nuclear buds was slightly though non-significantly increased after 48 h. Altogether, this indicates that in HPBCs BMAA is clastogenic and induces complex genomic alterations including structural chromosomal rearrangements and gene amplification. No influence on oxidative stress markers was noticed. These findings provide new evidence that environmental neurotoxin BMAA, in addition to targeting common pathways involved in neurodegeneration, can also induce genomic instability in non-target HPBCs suggesting that it might be involved in cancer development. Therefore, these data are important in advancing our current knowledge and opening new questions in the understanding of the mechanisms of BMAA toxicity, particularly in the context of genotoxicity. (C) 2018 Elsevier Ltd. All rights reserved.
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