Assessment of the mutagenic and genotoxic activity of cyanobacterial toxin beta-N-methyl-amino-L-alanine in Salmonella typhimurium

Novak, Matjaž; Hercog, Klara; Žegura, Bojana

doi:10.1016/j.toxicon.2016.04.047

Cited by 6 publications

(5 citation statements)

References 71 publications

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“…Hemocytes membranes might therefore also have amino-acid transporters that are able to get BMAA into the cell. So far, except for one study carried out on bacteria [ 48 ], toxicological studies about the impact of BMAA have been carried out on vertebrates, and the extrapolation of potential mechanisms of action on invertebrates remains tenuous. As BMAA is an emerging environmental neurotoxin, little evidence of animal toxicology is available to date, and its metabolites are also unknown; therefore, it may be difficult to assess if the observed damages where caused by this molecule or its metabolites.…”

Section: Discussionmentioning

confidence: 99%

“…DNA damages by BMAA could have been induced either indirectly on the genome or directly by crossing the nuclear membrane. An Ames test on five Salmonella typhimurium strains with five BMAA concentrations ranging from 11 to 900 µg/plate has shown that BMAA did not induce any mutation and was neither cytotoxic nor genotoxic for bacteria [ 48 ]. A study carried out on human neuroblastoma cell line SH-SY5Y [ 49 ] showed, through a plasmid assay, that BMAA is able to induce DNA strand breaks from 309.2 mg/L, potentially linked with the nitrosation of BMAA, which generates an alkylating form that is also able to induce more DNA strand breaks than BMAA itself.…”

Section: Discussionmentioning

confidence: 99%

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Genotoxic and Cytotoxic Effects on the Immune Cells of the Freshwater Bivalve Dreissena polymorpha Exposed to the Environmental Neurotoxin BMAA

Lepoutre

Milliote

Bonnard

et al. 2018

Toxins

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The environmental neurotoxin β-N-Methylamino-l-alanine (BMAA) has been pointed out to be involved in human neurodegenerative diseases. This molecule is known to be bioaccumulated by bivalves. However, little data about its toxic effects on freshwater mussels is available, particularly on the hemolymphatic compartment and its hemocyte cells involved in various physiological processes such as immune defenses, digestion and excretion, tissue repair, and shell production. Here we exposed Dreissena polymorpha to dissolved BMAA, at the environmental concentration of 7.5 µg of /mussel/3 days, during 21 days followed by 14 days of depuration in clear water, with the objective of assessing the BMAA presence in the hemolymphatic compartment, as well as the impact of the hemocyte cells in terms of potential cytotoxicity, immunotoxicity, and genotoxiciy. Data showed that hemocytes were in contact with BMAA. The presence of BMAA in hemolymph did not induce significant effect on hemocytes phagocytosis activity. However, significant DNA damage on hemocytes occurred during the first week (days 3 and 8) of BMAA exposure, followed by an increase of hemocyte mortality after 2 weeks of exposure. Those effects might be an indirect consequence of the BMAA-induced oxidative stress in cells. However, DNA strand breaks and mortality did not persist during the entire exposure, despite the BMAA persistence in the hemolymph, suggesting potential induction of some DNA-repair mechanisms.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Genotoxic and Cytotoxic Effects on the Immune Cells of the Freshwater Bivalve Dreissena polymorpha Exposed to the Environmental Neurotoxin BMAA

Lepoutre

Milliote

Bonnard

et al. 2018

Toxins

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“…BMAA showed no mutagenic, cytotoxic, or genotoxic effects on several strains of the heterotrophic bacterium Salmonella typhimurium [158]. At the same time, the photoautotrophic growth of cyanobacteria was inhibited by exogenous BMAA in micromolar amounts [104][105][106][107][108][109]159].…”

Section: Bmaa and Proteins: Misincorporation And Electrostatic Bindingmentioning

confidence: 93%

Non-Proteinogenic Amino Acid β-N-Methylamino-L-Alanine (BMAA): Bioactivity and Ecological Significance

Кокшарова

Safronova

2022

Toxins

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Research interest in a non-protein amino acid β-N-methylamino-L-alanine (BMAA) arose due to the discovery of a connection between exposure to BMAA and the occurrence of neurodegenerative diseases. Previous reviews on this topic either considered BMAA as a risk factor for neurodegenerative diseases or focused on the problems of detecting BMAA in various environmental samples. Our review is devoted to a wide range of fundamental biological problems related to BMAA, including the molecular mechanisms of biological activity of BMAA and the complex relationships between producers of BMAA and the environment in various natural ecosystems. At the beginning, we briefly recall the most important facts about the producers of BMAA (cyanobacteria, microalgae, and bacteria), the pathways of BMAA biosynthesis, and reliable methods of identification of BMAA. The main distinctive feature of our review is a detailed examination of the molecular mechanisms underlying the toxicity of BMAA to living cells. A brand new aspect, not previously discussed in any reviews, is the effect of BMAA on cyanobacterial cells. These recent studies, conducted using transcriptomics and proteomics, revealed potent regulatory effects of BMAA on the basic metabolism and cell development of these ancient photoautotrophic prokaryotes. Exogenous BMAA strongly influences cell differentiation and primary metabolic processes in cyanobacteria, such as nitrogen fixation, photosynthesis, carbon fixation, and various biosynthetic processes involving 2-oxoglutarate and glutamate. Cyanobacteria were found to be more sensitive to exogenous BMAA under nitrogen-limited growth conditions. We suggest a hypothesis that this toxic diaminoacid can be used by phytoplankton organisms as a possible allelopathic tool for controlling the population of cyanobacterial cells during a period of intense competition for nitrogen and other resources in various ecosystems.

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“…The mutant strains are placed and auxotrophic means for the amino acid which they can not synthesize, the compounds are considered to be mutagenic, if colonies are observed in the media. 12 In vitro test of DNA damage by Allium cepa test in low cost, easily handled, has advantages over other short-term tests, also enables the evaluation of different end points for chromosome aberrations and to detect genotoxicity. 13 This test has also been used for studying environmental toxicity as well as food preservatives.…”

Section: Toxicogenetics At Both the Transcriptional And Translationalmentioning

confidence: 99%

Current methodologies in assessing toxicity of natural products

Valle¹

2018

Int J Phytocos Nat Ingred

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Herbal ingredients and the combination of several species of plants, account for the different therapeutic and healing effects observed in the "complementary" or "alternative" medicine. The practice of herbal medicine is responsible for extense human knowledge that has developed over time in various cultures, worldwide. Cosmetics or nutracosmetics may cause adverse reactions in the skin, specially when there is a lack of cosmetic vigilance management. It is important to promote, in a relatively permissive regulatory environment, conscious efforts on the part of health professionals, to evaluate the outcomes and validate their pharmacological and cosmetic use. Traditional knowledge about the use of some herbs should be reevaluated and scientific basis should be considered. It is important to conduct a complete scientific research for validating herbal therapeutics and optimizing safety. Scientific toxicological research, using proper models, must continue to prove quality, efficacy, pharmacokinetics and pharmacodynamics interactions with other substances, and safety. Mechanisms of actions, as well as factors affecting toxicity should be studied, revised and taken in account to prevent adverse reactions, when using complementary or alternative medicine.

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Assessment of the mutagenic and genotoxic activity of cyanobacterial toxin beta-N-methyl-amino-L-alanine in Salmonella typhimurium

Cited by 6 publications

References 71 publications

Genotoxic and Cytotoxic Effects on the Immune Cells of the Freshwater Bivalve Dreissena polymorpha Exposed to the Environmental Neurotoxin BMAA

Genotoxic and Cytotoxic Effects on the Immune Cells of the Freshwater Bivalve Dreissena polymorpha Exposed to the Environmental Neurotoxin BMAA

Non-Proteinogenic Amino Acid β-N-Methylamino-L-Alanine (BMAA): Bioactivity and Ecological Significance

Current methodologies in assessing toxicity of natural products

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