Naslov
Genotoxic effects of neurotoxin beta-N- methylamino-L-alanine in human peripheral blood cells

Autori
Geric, Marko ; Gajski, Goran ; Domijan, Ana-Marija ; Garaj-Vrhovac, Vera ; Filipic, Metka ; Zegura, Bojana

Izvornik
Chemosphere (0045-6535) 214 (2019); 623-632

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

Ključne riječi
DNA damage ; Genotoxicity ; human blood cells ; non-target cells ; ß-N-methylamino-l-alanine

Sažetak
The non-proteinogenic amino acid ß-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 μg/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 h at 20 μg/mL and nucleoplasmic bridges after 48 h at 20 μg/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.

Izvorni jezik
Engleski

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