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Investigation of cyto-genotoxic effects of a food sweetener Acesulfame potassium

Yıl 2022, Cilt: 8 Sayı: 4, 273 - 283, 01.10.2022
https://doi.org/10.3153/FH22025

Öz

Acesulfame potassium (ACE-K) is an artificial sweetener widely used in many foods. This investigation assessed the cytotoxic effect of ACE-K using MTT assay in human hepatocellular carcinoma (HepG2) cell line and the genotoxic effect using chromosomal aberrations (CAs), micronucleus (MN), and comet assays in human lymphocytes. 7.5-240 μg/mL concentrations of ACE-K were applied to cells. ACE-K notably decreased the cell viability on HepG2 cells, especially at 120 and 240 μg/mL at 24 and 48 h. It also significantly reduced the mitotic index (MI) at 60, 120, and 240 μg/mL at both treatments (24 and 48 h) in human lymphocytes. The frequency of the CAs significantly increased at 60, 120, and 240 μg/mL for 48 h treatment compared to control. However, no difference was observed in the frequency of MN and nuclear division index (NDI) at all the treatments. ACE-K also induced comet tail length, tail intensity, and moment at 15 μg/mL in isolated human lymphocytes. Therefore, ACE-K showed a cytotoxic effect in HepG2 cells as well as human lymphocytes at higher concentrations. It also exhibits a mild genotoxic effect by increasing the frequency of CAs at long-term treatment and DNA damaging effect only at 15 μg/mL.

Destekleyen Kurum

This study was financially supported (except for comet assay) by Gazi University Scientific Research Projects Coordination Unit

Proje Numarası

64/2020-01.

Kaynakça

  • Ashok, I., Poornima, P.S., Wankhar, D., Ravindran, R., Sheeladevi, R. (2017). Oxidative stress evoked damages on rat sperm and attenuated antioxidant status on consumption of aspartame. International Journal of Impotence Research, 29(4), 164-170. https://doi.org/10.1038/ijir.2017.17
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  • Carocho, M., Morales, P., Ferreira, I.C. (2017). Sweeteners as food additives in the XXI century: A review of what is known, and what is to come. Food and Chemical Toxicology, 107, 302-317. https://doi.org/10.1016/j.fct.2017.06.046
  • Chappell, G.A., Wikoff, D.S., Doepker, C.L., Borghoff, S.J. (2020). Lack of potential carcinogenicity for acesulfame potassium–systematic evaluation and integration of mechanistic data into the totality of the evidence. Food and Chemical Toxicology, 141, 111375. https://doi.org/10.1016/j.fct.2020.111375
  • Chattopadhyay, S., Raychaudhuri, U., Chakraborty, R. (2014). Artificial sweeteners–a review. Journal of Food Science and Technology, 51(4), 611-621. https://doi.org/10.1007/s13197-011-0571-1
  • Choi, J.M., Oh, S.J., Lee, S.Y., Im, J.H., Oh, J.M., Ryu, C.S., et al. (2015). HepG2 cells as an in vitro model for evaluation of cytochrome P450 induction by xenobiotics. Archives of Pharmacal Research, 38(5), 691–704. https://doi.org/10.1007/s12272-014-0502-6 Cruz-Rojas, C., SanJuan Reyes, N., Fuentes Benites, M.P.A.G., Dublan García, O., Galar Martínez, M., Islas Flores, H, et al. (2019). Acesulfame potassium: Its ecotoxicity measured through oxidative stress biomarkers in common carp (Cyprinus carpio). Science of the Total Environment, 647, 772-784. https://doi.org/10.1016/j.scitotenv.2018.08.034
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  • Dong, G., Li, X., Han, G., Du, L., Li, M. (2020). Zebrafish neuro-behavioral profiles altered by acesulfame (ACE) within the range of “no observed effect concentrations (NOECs)”. Chemosphere, 243, 125431. https://doi.org/10.1016/j.chemosphere.2019.125431
  • Dusinska, M., Mariussen, E., Rundén Pran, E., Hudecova, A.M., Elje, E., Kazimirova, A., et al. (2019). In vitro approaches for assessing the genotoxicity of nanomaterials. Qunwei Zhang (ed.), Nanotoxicity: Methods and Protocols, Methods in Molecular Biology. Nature, 1894, 83-122. https://doi.org/10.1007/978-1-4939-8916-4_6
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  • Evans, H.J. (1984). Human peripheral blood lymphocytes for the analysis of chromosome aberrations in mutagentests in mutagen tests. In: B.J. Kilbey, M. Legator, W. Nichols, C. Ramel, (eds). Handbook of mutagenicity test procedures. Amsterdam: Elsevier Science Publishers, 405-427. https://doi.org/10.1016/B978-0-444-80519-5.50023-7
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  • Fowler, S.P., Williams, K., Resendez, R.G., Hunt, K., Hazuda, H.P., Stern, M.P. (2008). Fueling the obesity epidemic? Artificially sweetened beverage use and longterm weight gain. Obesity, 16(8), 1894-1900. https://doi.org/10.1038/oby.2008.284
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Yıl 2022, Cilt: 8 Sayı: 4, 273 - 283, 01.10.2022
https://doi.org/10.3153/FH22025

Öz

Proje Numarası

64/2020-01.

Kaynakça

  • Ashok, I., Poornima, P.S., Wankhar, D., Ravindran, R., Sheeladevi, R. (2017). Oxidative stress evoked damages on rat sperm and attenuated antioxidant status on consumption of aspartame. International Journal of Impotence Research, 29(4), 164-170. https://doi.org/10.1038/ijir.2017.17
  • Bach, D-H., Zhang, W., Sood, A.K. (2019). Chromosomal Instability in Tumor Initiation and Development. Cancer Research, 79(16), 3995–4002. https://doi.org/10.1158/0008-5472.CAN-18-3235
  • Bandyopadhyay, A., Ghoshal, S., Mukherjee, A. (2008). Genotoxicity testing of low-calorie sweeteners: aspartame, acesulfame-K, and saccharin. Drug and Chemical Toxicology, 31(4), 447-457. https://doi.org/10.1080/01480540802390270
  • Belton, K., Schaefer, E., Guiney, P.D. (2020). A review of the environmental fate and effects of acesulfame‐potassium. Integrated Environmental Assessment and Management, 16(4), 421-437. https://doi.org/10.1002/ieam.4248
  • Cao, Y., Liu, H., Qin, N., Ren, X., Zhu, B., Xiaodong, X. (2020). Impact of food additives on the composition and function of gut microbiota: A review. Trends in Food Science & Technology, 99, 295-310. https://doi.org/10.1016/j.tifs.2020.03.006
  • Carocho, M., Morales, P., Ferreira, I.C. (2017). Sweeteners as food additives in the XXI century: A review of what is known, and what is to come. Food and Chemical Toxicology, 107, 302-317. https://doi.org/10.1016/j.fct.2017.06.046
  • Chappell, G.A., Wikoff, D.S., Doepker, C.L., Borghoff, S.J. (2020). Lack of potential carcinogenicity for acesulfame potassium–systematic evaluation and integration of mechanistic data into the totality of the evidence. Food and Chemical Toxicology, 141, 111375. https://doi.org/10.1016/j.fct.2020.111375
  • Chattopadhyay, S., Raychaudhuri, U., Chakraborty, R. (2014). Artificial sweeteners–a review. Journal of Food Science and Technology, 51(4), 611-621. https://doi.org/10.1007/s13197-011-0571-1
  • Choi, J.M., Oh, S.J., Lee, S.Y., Im, J.H., Oh, J.M., Ryu, C.S., et al. (2015). HepG2 cells as an in vitro model for evaluation of cytochrome P450 induction by xenobiotics. Archives of Pharmacal Research, 38(5), 691–704. https://doi.org/10.1007/s12272-014-0502-6 Cruz-Rojas, C., SanJuan Reyes, N., Fuentes Benites, M.P.A.G., Dublan García, O., Galar Martínez, M., Islas Flores, H, et al. (2019). Acesulfame potassium: Its ecotoxicity measured through oxidative stress biomarkers in common carp (Cyprinus carpio). Science of the Total Environment, 647, 772-784. https://doi.org/10.1016/j.scitotenv.2018.08.034
  • De Koning, L., Malik, V.S., Rimm, E.B., Willett, W.C., Hu, F.B., (2011). Sugar-sweetened and artificially sweetened beverage consumption and risk of type 2 diabetes in men. The American Journal of Clinical Nutrition, 93, 1321-1327. https://doi.org/10.3945/ajcn.110.007922
  • Dong, G., Li, X., Han, G., Du, L., Li, M. (2020). Zebrafish neuro-behavioral profiles altered by acesulfame (ACE) within the range of “no observed effect concentrations (NOECs)”. Chemosphere, 243, 125431. https://doi.org/10.1016/j.chemosphere.2019.125431
  • Dusinska, M., Mariussen, E., Rundén Pran, E., Hudecova, A.M., Elje, E., Kazimirova, A., et al. (2019). In vitro approaches for assessing the genotoxicity of nanomaterials. Qunwei Zhang (ed.), Nanotoxicity: Methods and Protocols, Methods in Molecular Biology. Nature, 1894, 83-122. https://doi.org/10.1007/978-1-4939-8916-4_6
  • Erikel, E., Yuzbasioglu, D., Unal, F. (2020). Genotoxic and antigenotoxic potential of amygdalin on isolated human lymphocytes by the comet assay. Journal of Food Biochemistry, 44(10), e13436. https://doi.org/10.1111/jfbc.13436
  • Eroglu, Y., Eroglu, H.E., Ilbas, A.I. (2007). Gamma ray reduces mitotik index in embriyonic roots of Hordeum vulgare L. Advanced Biomedical Research, 1(2), 26-28.
  • Evans, H.J. (1984). Human peripheral blood lymphocytes for the analysis of chromosome aberrations in mutagentests in mutagen tests. In: B.J. Kilbey, M. Legator, W. Nichols, C. Ramel, (eds). Handbook of mutagenicity test procedures. Amsterdam: Elsevier Science Publishers, 405-427. https://doi.org/10.1016/B978-0-444-80519-5.50023-7
  • Fenech M. (2000). The in vitro micronucleus technique. Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis, 455(1-2), 81-95. https://doi.org/10.1016/S0027-5107(00)00065-8
  • Fenech, M., Knasmueller, S., Bolognesi, C., Holland, N., Bonassi, S., Kirsch-Volders, M. (2020). Micronuclei as biomarkers of DNA damage, aneuploidy, inducers of chromosomal hypermutation and as sources of pro-inflammatory DNA in humans. Mutation Research/Reviews in Mutation Research, 786, 108342. https://doi.org/10.1016/j.mrrev.2020.108342
  • Fındıklı, Z., Türkoglu, S., (2014). Determination of the effects of some artificial sweeteners on human peripheral lymphocytes using the comet assay. Journal of Toxicology and Environmental Health Sciences, 6(8), 147-153. https://doi.org/10.5897/JTEHS2014.0313
  • Fowler, S.P., Williams, K., Resendez, R.G., Hunt, K., Hazuda, H.P., Stern, M.P. (2008). Fueling the obesity epidemic? Artificially sweetened beverage use and longterm weight gain. Obesity, 16(8), 1894-1900. https://doi.org/10.1038/oby.2008.284
  • Fowler, S.P.G., (2016). Low-calorie sweetener use and energy balance: Results from experimental studies in animals, and large-scale prospective studies in humans. Physiology Behavior, 164, 517-523. https://doi.org/10.1016/j.physbeh.2016.04.047
  • Fung, T.T., Malik, V., Rexrode, K.M., Manson, J.E., Willett, W.C., Hu, F.B. (2009). Sweetened beverage consumption and risk of coronary heart disease in women. The American Journal of Clinical Nutrition, 89(4), 1037-1042. https://doi.org/10.3945/ajcn.2008.27140
  • Heredia-García, G., Gómez Oliván, L.M., Orozco Hernández, J.M., Luja Mondragón, M., Islas Flores, H., Juan Reyes, N. S., Galar-Martínez M., García-Medina, S., Dublán-García, O. (2019). Alterations to DNA, apoptosis and oxidative damage induced by sucralose in blood cells of Cyprinus carpio. Science of the Total Environment, 692, 411-421. https://doi.org/10.1016/j.scitotenv.2019.07.165
  • Hernández-Pérez, A.F., Jofre, F.M., Queiroz, S., de Arruda, P.V., Chandel, A.K., Graç, M.D., Almeida, F. (2020). Chapter 9: Biotechnological production of sweeteners. Verma, M., Chandel, A., (Eds). Biotechnological Production of Bioactive Compounds, Publisher: Elsevier, 261-292. https://doi.org/10.1016/B978-0-444-64323-0.00009-6
  • Ibi, D., Suzuki, F., Hiramatsu, M. (2018). Effect of AceK (acesulfame potassium) on brain function under dietary restriction in mice. Physiology & Behavior, 188, 291-297. https://doi.org/10.1016/j.physbeh.2018.02.024
  • Jain, A.K., Sorbhoy, R.K. (1988). Cytogenetical studies on the effects of some chlorinated pesticides. III. Concluding remarks. Cytologia, 53(3), 427-436. https://doi.org/10.1508/cytologia.53.427
  • Jeffrey, A.M., Williams, G.M. (2000). Lack of DNA-damaging activity of five non-nutritive sweeteners in the rat hepatocyte/DNA repair assay. Food and Chemical Toxicology, 38(4), 335-338. https://doi.org/10.1016/S0278-6915(99)00163-5
  • Joint FAO/WHO Expert Committee on Food Additives (JECFA), (1991). Thirty‐ seventh report of the Joint FAO/WHO Expert Committee on Food Additives (JECFA). Geneva (CH). WHO Technical Report Series, No: 806, 20.
  • Kokotou, M.G., Asimakopoulos, A.G., Thomaidis, N.S. (2012). Artificial sweeteners as emerging pollutants in the environment: analytical methodologies and environmental impact. Analytical Methods, 4(10), 3057-3070. https://doi.org/10.1039/c2ay05950a
  • Li, D., O'Brien, J.W., Tscharke, B.J., Choi, P.M., Zheng, Q., Ahmed, F., et al. (2020). National wastewater reconnaissance of artificial sweetener consumption and emission in Australia. Environment International, 143, 105963. https://doi.org/10.1016/j.envint.2020.105963
  • Lindseth, G.N., Coolahan, S.E., Petros, T.V., Lindseth, P.D. (2014). Neurobehavioral effects of aspartame consumption. Research in Nursing & Health, 37(3), 185-193. https://doi.org/10.1002/nur.21595
  • Lutsey, P.L., Steffen, L.M., Stevens, J. (2008). Dietary intake and the development of the metabolic syndrome. Circulation, 117(6), 754-761. https://doi.org/10.1161/CIRCULATIONAHA.107.716159
  • Magnuson, B.A., Carakostas, M.C., Moore, N.H., Poulos, S.P., Renwick, A.G., (2016). Biological fate of low-calorie sweeteners. Nutrition Reviews, 74(11), 670-689. https://doi.org/10.1093/nutrit/nuw032
  • Mamur, S, Yuzbasioglu D, Yılmaz S, Erikel E, Unal F. (2018). Assessment of Cytotoxic and Genotoxic Effects of Enniatin-A In Vitro. Food Additives and Contaminants-Part A, 35(8), 1633-1644. https://doi.org/10.1080/19440049.2018.1486513
  • Mossman, T. (1983). Rapid colometric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. Journal Immunol Methods, 65, 55-63. https://doi.org/10.1016/0022-1759(83)90303-4
  • Mukherjee, A., Chakrabarti, J. (1997). In vivo cytogenetic studies on mice exposed to acesulfame-K—a non-nutritive sweetener. Food and Chemical Toxicology, 35(12), 1177-1179. https://doi.org/10.1016/S0278-6915(97)85469-5
  • Mukhopadhyay, M., Mukherjee, A., Chakrabarti, J. (2000). In vivo cytogenetic studies on blends of aspartame and acesulfame-K. Food and Chemical Toxicology, 38(1), 75-77. https://doi.org/10.1016/S0278-6915(99)00115-5
  • Najam, K., Altaf, I., Ashraf, M., Rasheed, M.A., Saleem, F., Munir, N., et al. (2017). In vitro evaluation of mutagenicity and genotoxicity of sitagliptin alone and in combination with artificial sweeteners. Tropical Journal of Pharmaceutical Research, 16(8), 1841-1847. https://doi.org/10.4314/tjpr.v16i8.13
  • Oldfield, L.E., Roy, J.W., Robinson, C.E. (2020). Investigating the use of the artificial sweetener acesulfame to evaluate septic system inputs and their nutrient loads to streams at the watershed scale. Journal of Hydrology, 587, 124918. https://doi.org/10.1016/j.jhydrol.2020.124918
  • Palus, J., Rydzynski, K., Dziubaltowska, E., Wyszynska, K., Natarajan, A.T., Nilsson, R., et al. (2003). Genotoxic effects of occupational exposure to lead and cadmium. Mutation Research/Genetic Toxicology and Environmental Mutagenesis, 540(1), 19-28. https://doi.org/10.1016/S1383-5718(03)00167-0
  • Pintor, A.V.B., Queiroz, L.D., Barcelos, R., Primo, L.S.G., Maia, L.C., Alves, G.G. (2020). MTT versus other cell viability assays to evaluate the biocompatibility of root canal filling materials: a systematic review. International Endodontic Journal, 53(10), 1348-1373. https://doi.org/10.1111/iej.13353
  • Schiano, C., Grimaldi, V., Scognamiglioi M., Costa, D., Soricelli, A., Nicoletti, G.F., et al. (2021). Soft drinks and sweeteners intake: Possible contribution to the development of metabolic syndrome and cardiovascular diseases. Beneficial or detrimental action of alternative sweeteners?. Food Research International, 142, 110220. https://doi.org/10.1016/j.foodres.2021.110220
  • Setayesh, T., Kundi, M., Nersesyan, A., Stopper, H., Fenech, M., Krupitza, G. et al. (2020). Use of micronucleus assays for the prediction and detection of cervical cancer: a meta-analysis. Carcinogenesis, 41(10), 1318-1328. https://doi.org/10.1093/carcin/bgaa087
  • Silva, M.R., Moya, C.Á., León, A.G.S., Velasco, R.R., Flores, A.M.C. (2018). Genotoxic activity of saccharin, acesulfame-K, stevia and aspartame-acesulfame-K in commercial form. Journal of Clinical Toxicology, 8(385), 2161-0495. https://doi.org/10.4172/2161-0495.1000385
  • Singh, N., Lubana, S.S., Arora, S., Sachmechi, I. (2020). A study of artificial sweeteners and thyroid cancer risk. Journal of Clinical Medicine Research, 12(8), 492. https://doi.org/10.14740/jocmr4258
  • Singh, N.P., McCoy, M.T., Tice, R.R., Schneider, E.L. (1988). A simple technique forquantitation of low levels of DNA damage in individual cells. Experimental Cell Research, 175(1), 184-191. https://doi.org/10.1016/0014-4827(88)90265-0
  • Soffritti, M., Belpoggi, F., Esposti, D.D., Lambertini, L., Tibaldi, E., Rigano, A. (2006). First experimental demonstration of the multipotential carcinogenic effects of aspartame administered in the feed to Sprague-Dawley rats. Environmental Health Perspectives, 114(3), 379-385. https://doi.org/10.1289/ehp.8711
  • Souza, A.C.F., Yujra, V.Q., Pisani, L.P., Viana, de M.D.B., De Castro, G.M., Ribeiro, D.A. (2019). The use of single-cell comet assay on oral cells: a critical review. Anticancer Research, 39(8), 4011-4017. https://doi.org/10.21873/anticanres.13556
  • Stice, S.A., Beedanagari, S.R., Vulimiri, S.V., Bhatia, S.P., Mahadevan, B. (2019). Chapter 44: Genotoxicity Biomarkers: Molecular Basis of Genetic Variability and Susceptibility. In Biomarkers in Toxicology. Gupta, R., (Edt), Second Edition, Academic Press, 807-821. https://doi.org/10.1016/B978-0-12-814655-2.00044-X
  • Sturgeon, S.R., Hartge, P., Silverman, D.T., Kantor, A.F., Linehan, W.M., Lynch C., et al. (1994). Associations between bladder cancer risk factors and tumor stage and grade at diagnosis. Epidemiology, 5, 218-225. https://doi.org/10.1097/00001648-199403000-00012
  • Surrales, J., Xamena, N., Creus, A., Catalan, J., Norppa, H., Marcos, R. (1995). Induction of micronuclei by five pyrethroid insecticides in whole blood and isolated human lymphocytes cultures. Mutation Research/Genetic Toxicology, 341(3), 169-184. https://doi.org/10.1016/0165-1218(95)90007-1 van Eyk, A.D. (2015). The effect of five artificial sweeteners on Caco-2, HT-29 and HEK-293 cells. Drug and Chemical Toxicology, 38(3), 318-327. https://doi.org/10.3109/01480545.2014.966381
  • van Tonder, A., Joubert, A.M., Cromarty, A.D. (2015). Limitations of the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay when compared to three commonly used cell enumeration assays. BMC Research Notes, 8(1), 1-10. https://doi.org/10.1186/s13104-015-1000-8
  • Vodicka, P., Musak, L., Vodickova, L., Vodenkova, S., Catalano, C., Kroupa, M., et al. (2018). Genetic variation of acquired structural chromosomal aberrations. Mutation Research/Genetic Toxicology and Environmental Mutagenesis, 836, 13-21. https://doi.org/10.1016/j.mrgentox.2018.05.014
  • Whitehouse, C.R., Boullata, J., McCauley, L.A. (2008). The potential toxicity of artificial sweeteners. Aaohn Journal, 56(6), 251–261. https://doi.org/10.1177/216507990805600604
  • World Health Organization (WHO), (1980). Toxicological evaluation of certain food additives. WHO Food Additives Series No 496. 16, 11.
  • Yang, Y., Liu, Z., Zheng, H., Zhu, S., Zhang, K., Li, X., et al. (2021). Sucralose, a persistent artificial sweetener in the urban water cycle: insights into occurrence, chlorinated byproducts formation, and human exposure. Journal of Environmental Chemical Engineering, 9(4), 105293. https://doi.org/10.1016/j.jece.2021.105293
  • Yuzbasioglu, D., Mahmoud, J. H., Mamur, S., Ünal, F. (2022). Cytogenetic effects of antidiabetic drug metformin. Drug and Chemical Toxicology, 45(2), 955-962. https://doi.org/10.1080/01480545.2020.1844226
Toplam 56 adet kaynakça vardır.

Ayrıntılar

Birincil Dil İngilizce
Konular Yapısal Biyoloji
Bölüm Research Articles
Yazarlar

Sevcan Mamur 0000-0002-8615-5331

Deniz Yüzbaşıoğlu 0000-0003-2756-7712

Sabire Nur Bülbül 0000-0002-6897-793X

Fatma Ünal 0000-0002-7468-6186

Proje Numarası 64/2020-01.
Yayımlanma Tarihi 1 Ekim 2022
Gönderilme Tarihi 7 Haziran 2022
Yayımlandığı Sayı Yıl 2022Cilt: 8 Sayı: 4

Kaynak Göster

APA Mamur, S., Yüzbaşıoğlu, D., Bülbül, S. N., Ünal, F. (2022). Investigation of cyto-genotoxic effects of a food sweetener Acesulfame potassium. Food and Health, 8(4), 273-283. https://doi.org/10.3153/FH22025

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