Research Article
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Genotoxic and Cytotoxic Activity of Cyanobacterial (Blue-Green Algal) Toxin BMAA in Human Lymphocyte Cells

Year 2019, Volume: 1 Issue: 1, 8 - 14, 30.08.2019

Abstract

Cyanobacteria, one of the
oldest life forms, are also known as blue-green algae. Many species of cyanobacteria
produce metabolites called cyanotoxin, which are classified as hepatotoxins,
neurotoxins and cytotoxins and are highly toxic to vertebrate organisms. One of
these toxins is the Beta-N-methyl-amino-L-alanine (BMAA). Blooms (large numbers
or colonies) of the cyanobacteria or related organisms produce one or more toxins
that can be dangerous to fish, wild animals and humans. There is not
enough information in the literature related to the genotoxic effect of this
toxin. In this study, it was aimed to determine investigation of the cytotoxic
and genotoxic activity of cyanobacterial toxin BMAA in human lymphocyte cells
by micronucleus assay. Different concentrations (20, 10, 5 and 1 μg/ml) of BMAA
cyanotoxin were applied to human lymphocyte cell culture and micronucleus
frequencies (MN) and nuclear division index (NDI) were calculated to determine
genotoxic and cytotoxic effects. The data obtained from our study were compared
with the negative control group prepared with dimethyl sulfoxide (DMSO) and
with the well known ethyl methanesulfonate (EMS) with genotoxic effect and
positive control group. According to these results; increasing the frequency of
micronucleus according to the whole control negative control group that we used
BMAA was not statistically significant compared with the EMS (positive control
group) (p>0.05). However, no significant cytotoxic effect was found when the
results of the NDI were examined (p>0.05). 

Supporting Institution

Amasya University

Project Number

FMB-BAP 16-0205

References

  • Al-Sammak, M.A. 2012. Occurrence and effect of algal neurotoxins in Nebraska freshwater ecosystems. PhD. Thesis. University of Nebraska-Lincoln, USA.
  • Buenz, E. J., and Howe, C.L. 2007. Beta-methylarnino-alanine (BMAA) injures hippocampal neurons in vivo. Neurotoxicology, 28(3): 702-704.
  • Chang, Y.C., Chiu, S.-J., and Kao, K.P. 1993. Beta-N-methylamino-L-alanine (L-BMAA) decreases brain glutamate receptor number and induces behavioral changes in rats. The Chinese journal of physiology, 36(2): 79-84.
  • Cox, P.A., Kostrzewa, R.M., Guillemin, G.J. 2017. BMAA and neurodegenerative illness. Neurotox. Res.,1: 1-6.
  • Dawson, R., Marschall, E.G., Chan, K.C., Millard, W.J., Eppler, B., and Patterson, T.A. 1998. Neurochemical and neurobehavioral effects of neonatal administration of β-N-methylamino-l-alanine and 3,3'-iminodipropionitrile. Neurotoxicology and Teratology, 20(2): 181-192.
  • de Munck, E., Muñoz-Sáez, E., Miguel, B.G., Solas, M.T., Ojeda, I., Martínez, A., et al. 2013. β-N-methylamino-l-alanine causes neurological and pathological phenotypes mimicking Amyotrophic Lateral Sclerosis (ALS): The first step towards an experimental model for sporadic ALS. Environmental toxicology and pharmacology, 36(2): 243-255.
  • Esterhuizen-Londt, M., Pflugmacher, S., and Downing, T.G. 2011. β-N-Methylamino-L-alanine (BMAA) uptake by the aquatic macrophyte Ceratophyllum demersum. Ecotoxicology and Environmental Safety, 74(1): 74-77.
  • Esterhuizen-Londt, M., Pflugmacher, S., and Downing, T.G. 2011b. The effect of β-N-methylamino-L-alanine (BMAA) on oxidative stress response enzymes of the macrophyte Ceratophyllum demersum. Toxicon, 57(5): 803-810.
  • Fenech, M. 2000. The In vitro micronucleus technique. Mutation Research, 455 (1-2): 81-95.
  • Fleming L.E., Rivero C., Burns J., Willams C., Bean J.A., Shea K.A., Stinn J. 2002. Blue green algal (cyanobacterial) toxins, surface drinking water, and liver cancer in Florida. Harmful Algae, 1: 157-168.
  • Geh, E.N., Armah, A., Ghosh, D., Stelma, G., & Bernstein, J.A. 2016. Sensitization of a child to Cyanobacteria after recreational swimming in a lake. Journal of Allergy and Clinical Immunology, 137(6): 1902-1904.
  • Gibbons, C.F., & LeBaron, M. J. 2017. Applied genetic toxicology: From principles to practice. Environmental and molecular mutagenesis, 58(5): 232-234.
  • Güven, G.S., Cuna, T., Birinci, N., Güven, M., Onaran, İ. , Hacıhanefioğlu, S. ,Ulutin, T. 2006. 17- β Estradiole ile İndüklenen İnsan Lenfositlerindeki Mikronükleus Sıklığının İncelenmesi. Cerrahpaşa Tıp Dergisi, 37: 10-13.
  • Jonasson, S., Eriksson, J., Berntzon, L., Rasmussen, U., and Bergman, B. 2008. A novel cyanobacterial toxin (BMAA) with potential neurodegenerative effects. Plant biotechnology, 25(3): 227-232.
  • Karlsson, O., Berg, A. L., Lindstrom, A.K., Hanrieder, J., Arnerup, G., Roman, E., et al. 2012. Neonatal exposure to the cyanobacterial toxin BMAA induces changes in protein expression, and neurodegeneration in adult hippocampus. Toxicological Sciences, 130(2): 391-404.
  • Karlsson, O., Lindquist, N.G., Brittebo, E.B., and Roman, E. 2009a. Selective brain uptake and behavioral effects of the cyanobacterial toxin BMAA (β-N-methylamino-l-alanine) following neonatal administration to rodents. Toxicological Sciences, 109(2): 286-295.
  • Karlsson, O., Roman, E., and Brittebo, E.B. 2009b. Long-term cognitive impairments inadult rats treated neonatally with β-N-methylamino-L-alanine Toxicological Sciences, 112(1): 185-195.
  • Karlsson, O., Roman, E., Berg, A.L., and Brittebo, E.B. 2011. Early hippocampal cell death, and late learning and memory deficits in rats exposed to the environmental toxin BMAA (β-N-methylamino-L-alanine) during the neonatal period. Behavioural Brain Research, 219(2): 310-320.
  • Lürling, M., Faassen, E.J., and Van Eenennaam, J.S. 2011. Effects of the cyanobacterial neurotoxin β-N-methylamino-L-alanine (BMAA) on the survival, mobility and reproduction of Daphnia magna. Journal of Plankton Research, 33(2): 333-342.
  • Matsuoka, Y., Rakonczay, Z., Giacobini, E., and Naritoku, D. (1993). L-beta-methylamino-alanine-induced behavioral changes in rats. Pharmacology Biochemistry and Behavior, 44(3): 727-734.
  • Melo Cavalcante, A.A., Rubensam, G., Picada, J.N., Gomes da Silva, E., Fonseca Moreira, J.C., & Henriques, J.A. 2003. Mutagenicity, antioxidant potential and antimutagenic activity against hydrogen peroxide of cashew (Anacardium occidentale) apple juice and cajuina. Environmental and molecular mutagenesis, 41(5): 360-369.
  • Novak, M., Hercog, K., & amp; Egura, B. 2016. Assessment of the mutagenic and genotoxic activity of cyanobacterial toxin beta-N-methyl-amino-L-alanine in Salmonella typhimurium. Toxicon, 118: 134-140.
  • Okle, O., Rath, L., Galizia, C.G., and Dietrich, D.R. 2013. The cyanobacterial neurotoxin beta-N-methylamino-L-alanine (BMAA) induces neuronal and behavioral changes in honey bees. Toxicology and Applied Pharmacology, 270(1): 9-15.
  • Purdie, E.L., Samsudin, S., Eddy, F.B., and Codd, G.A. 2009. Effects of the cyanobacterial neurotoxin β-N-methylamino-L-alanine on the early-life stage development of zebrafish (Danio rerio). Aquatic Toxicology, 95(4): 279-284.
  • Santucci, S., Zsurger, N., and Chabry, J. 2009. β-N-methylamino-l-alanine induced in vivo retinal cell death. Journal of Neurochemistry, 109(3): 819-825.
  • Şekeroğlu, V., & Atlı-Şekeroğlu, Z. (2011). Genotoksik hasarın belirlenmesinde mikronükleus testi. Turk Hij Den Biyol Derg, 68(4): 241-252.
  • Smith, S.E., and Meldrum, B.S. 1990. Receptor site specificity for the acute effects of β-N-methylamino-alanine in mice. European Journal of Pharmacology, 187(1): 131-134.
  • Svirčev, Z.B., Tokodi, N., Drobac, D., & Codd, G.A. 2014. Cyanobacteria in aquatic ecosystems in Serbia: effects on water quality, human health and biodiversity. Systematics and biodiversity, 12(3): 261-270.
  • Young, R.R. 2002. Genetic toxicology: web resources. Toxicology, 173(1-2): 103-121.
  • Zeiger, E. 2004. History and rationale of genetic toxicity testing: an impersonal, and sometimes personal, view. Environmental and molecular mutagenesis, 44(5): 363-371.
  • Zhou, X.C., Escala, W., Papapetropoulos, S., Bradley, W.G., and Zhai, R.G. 2009. BMAA neurotoxicity in Drosophila. Amyotrophic Lateral Sclerosis, 10(S2): 61-66.
  • Zhou, X.C., Escala, W., Papapetropoulos, S., and Zhai, R.G. 2010. β-N-methylamino-L-alanine induces neurological deficits and shortened life span in Drosophila. Toxins, 2(11): 2663-2679.
Year 2019, Volume: 1 Issue: 1, 8 - 14, 30.08.2019

Abstract

Project Number

FMB-BAP 16-0205

References

  • Al-Sammak, M.A. 2012. Occurrence and effect of algal neurotoxins in Nebraska freshwater ecosystems. PhD. Thesis. University of Nebraska-Lincoln, USA.
  • Buenz, E. J., and Howe, C.L. 2007. Beta-methylarnino-alanine (BMAA) injures hippocampal neurons in vivo. Neurotoxicology, 28(3): 702-704.
  • Chang, Y.C., Chiu, S.-J., and Kao, K.P. 1993. Beta-N-methylamino-L-alanine (L-BMAA) decreases brain glutamate receptor number and induces behavioral changes in rats. The Chinese journal of physiology, 36(2): 79-84.
  • Cox, P.A., Kostrzewa, R.M., Guillemin, G.J. 2017. BMAA and neurodegenerative illness. Neurotox. Res.,1: 1-6.
  • Dawson, R., Marschall, E.G., Chan, K.C., Millard, W.J., Eppler, B., and Patterson, T.A. 1998. Neurochemical and neurobehavioral effects of neonatal administration of β-N-methylamino-l-alanine and 3,3'-iminodipropionitrile. Neurotoxicology and Teratology, 20(2): 181-192.
  • de Munck, E., Muñoz-Sáez, E., Miguel, B.G., Solas, M.T., Ojeda, I., Martínez, A., et al. 2013. β-N-methylamino-l-alanine causes neurological and pathological phenotypes mimicking Amyotrophic Lateral Sclerosis (ALS): The first step towards an experimental model for sporadic ALS. Environmental toxicology and pharmacology, 36(2): 243-255.
  • Esterhuizen-Londt, M., Pflugmacher, S., and Downing, T.G. 2011. β-N-Methylamino-L-alanine (BMAA) uptake by the aquatic macrophyte Ceratophyllum demersum. Ecotoxicology and Environmental Safety, 74(1): 74-77.
  • Esterhuizen-Londt, M., Pflugmacher, S., and Downing, T.G. 2011b. The effect of β-N-methylamino-L-alanine (BMAA) on oxidative stress response enzymes of the macrophyte Ceratophyllum demersum. Toxicon, 57(5): 803-810.
  • Fenech, M. 2000. The In vitro micronucleus technique. Mutation Research, 455 (1-2): 81-95.
  • Fleming L.E., Rivero C., Burns J., Willams C., Bean J.A., Shea K.A., Stinn J. 2002. Blue green algal (cyanobacterial) toxins, surface drinking water, and liver cancer in Florida. Harmful Algae, 1: 157-168.
  • Geh, E.N., Armah, A., Ghosh, D., Stelma, G., & Bernstein, J.A. 2016. Sensitization of a child to Cyanobacteria after recreational swimming in a lake. Journal of Allergy and Clinical Immunology, 137(6): 1902-1904.
  • Gibbons, C.F., & LeBaron, M. J. 2017. Applied genetic toxicology: From principles to practice. Environmental and molecular mutagenesis, 58(5): 232-234.
  • Güven, G.S., Cuna, T., Birinci, N., Güven, M., Onaran, İ. , Hacıhanefioğlu, S. ,Ulutin, T. 2006. 17- β Estradiole ile İndüklenen İnsan Lenfositlerindeki Mikronükleus Sıklığının İncelenmesi. Cerrahpaşa Tıp Dergisi, 37: 10-13.
  • Jonasson, S., Eriksson, J., Berntzon, L., Rasmussen, U., and Bergman, B. 2008. A novel cyanobacterial toxin (BMAA) with potential neurodegenerative effects. Plant biotechnology, 25(3): 227-232.
  • Karlsson, O., Berg, A. L., Lindstrom, A.K., Hanrieder, J., Arnerup, G., Roman, E., et al. 2012. Neonatal exposure to the cyanobacterial toxin BMAA induces changes in protein expression, and neurodegeneration in adult hippocampus. Toxicological Sciences, 130(2): 391-404.
  • Karlsson, O., Lindquist, N.G., Brittebo, E.B., and Roman, E. 2009a. Selective brain uptake and behavioral effects of the cyanobacterial toxin BMAA (β-N-methylamino-l-alanine) following neonatal administration to rodents. Toxicological Sciences, 109(2): 286-295.
  • Karlsson, O., Roman, E., and Brittebo, E.B. 2009b. Long-term cognitive impairments inadult rats treated neonatally with β-N-methylamino-L-alanine Toxicological Sciences, 112(1): 185-195.
  • Karlsson, O., Roman, E., Berg, A.L., and Brittebo, E.B. 2011. Early hippocampal cell death, and late learning and memory deficits in rats exposed to the environmental toxin BMAA (β-N-methylamino-L-alanine) during the neonatal period. Behavioural Brain Research, 219(2): 310-320.
  • Lürling, M., Faassen, E.J., and Van Eenennaam, J.S. 2011. Effects of the cyanobacterial neurotoxin β-N-methylamino-L-alanine (BMAA) on the survival, mobility and reproduction of Daphnia magna. Journal of Plankton Research, 33(2): 333-342.
  • Matsuoka, Y., Rakonczay, Z., Giacobini, E., and Naritoku, D. (1993). L-beta-methylamino-alanine-induced behavioral changes in rats. Pharmacology Biochemistry and Behavior, 44(3): 727-734.
  • Melo Cavalcante, A.A., Rubensam, G., Picada, J.N., Gomes da Silva, E., Fonseca Moreira, J.C., & Henriques, J.A. 2003. Mutagenicity, antioxidant potential and antimutagenic activity against hydrogen peroxide of cashew (Anacardium occidentale) apple juice and cajuina. Environmental and molecular mutagenesis, 41(5): 360-369.
  • Novak, M., Hercog, K., & amp; Egura, B. 2016. Assessment of the mutagenic and genotoxic activity of cyanobacterial toxin beta-N-methyl-amino-L-alanine in Salmonella typhimurium. Toxicon, 118: 134-140.
  • Okle, O., Rath, L., Galizia, C.G., and Dietrich, D.R. 2013. The cyanobacterial neurotoxin beta-N-methylamino-L-alanine (BMAA) induces neuronal and behavioral changes in honey bees. Toxicology and Applied Pharmacology, 270(1): 9-15.
  • Purdie, E.L., Samsudin, S., Eddy, F.B., and Codd, G.A. 2009. Effects of the cyanobacterial neurotoxin β-N-methylamino-L-alanine on the early-life stage development of zebrafish (Danio rerio). Aquatic Toxicology, 95(4): 279-284.
  • Santucci, S., Zsurger, N., and Chabry, J. 2009. β-N-methylamino-l-alanine induced in vivo retinal cell death. Journal of Neurochemistry, 109(3): 819-825.
  • Şekeroğlu, V., & Atlı-Şekeroğlu, Z. (2011). Genotoksik hasarın belirlenmesinde mikronükleus testi. Turk Hij Den Biyol Derg, 68(4): 241-252.
  • Smith, S.E., and Meldrum, B.S. 1990. Receptor site specificity for the acute effects of β-N-methylamino-alanine in mice. European Journal of Pharmacology, 187(1): 131-134.
  • Svirčev, Z.B., Tokodi, N., Drobac, D., & Codd, G.A. 2014. Cyanobacteria in aquatic ecosystems in Serbia: effects on water quality, human health and biodiversity. Systematics and biodiversity, 12(3): 261-270.
  • Young, R.R. 2002. Genetic toxicology: web resources. Toxicology, 173(1-2): 103-121.
  • Zeiger, E. 2004. History and rationale of genetic toxicity testing: an impersonal, and sometimes personal, view. Environmental and molecular mutagenesis, 44(5): 363-371.
  • Zhou, X.C., Escala, W., Papapetropoulos, S., Bradley, W.G., and Zhai, R.G. 2009. BMAA neurotoxicity in Drosophila. Amyotrophic Lateral Sclerosis, 10(S2): 61-66.
  • Zhou, X.C., Escala, W., Papapetropoulos, S., and Zhai, R.G. 2010. β-N-methylamino-L-alanine induces neurological deficits and shortened life span in Drosophila. Toxins, 2(11): 2663-2679.
There are 32 citations in total.

Details

Primary Language English
Journal Section Research Articles
Authors

Arif Ayar 0000-0001-7849-4459

Deniz Altun Colak

Handan Uysal

Vahit Konar This is me

Project Number FMB-BAP 16-0205
Publication Date August 30, 2019
Submission Date July 29, 2019
Published in Issue Year 2019 Volume: 1 Issue: 1

Cite

APA Ayar, A., Altun Colak, D., Uysal, H., Konar, V. (2019). Genotoxic and Cytotoxic Activity of Cyanobacterial (Blue-Green Algal) Toxin BMAA in Human Lymphocyte Cells. Sabuncuoglu Serefeddin Health Sciences, 1(1), 8-14.