Araştırma Makalesi
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Aspartame-Induced Mitochondrial DNA Damage in Drosophila

Yıl 2018, , 129 - 135, 25.04.2018
https://doi.org/10.29048/makufebed.377982

Öz

Artificial sweeteners
are added to many products sold in the market today, such as food, beverages,
medicines, hygiene products. The possible toxic effects of any of these
products, because they are used by many people in the community, can pose a
risk for public health. DNA mutations generated by some artificial sweeteners
have been investigated by some researchers but there is no information in the
literature about the effects of these substances on mtDNA.
mtDNA
damage potentially is more important than deletions in nDNA because the whole
mitochondrial genome is expressed without intron regions. Also, somatic mtDNA
mutations have been increasingly observed in primary human cancers.
The aim of the current study, detection of the effects of some
artificial sweeteners on mtDNA damage and copy number in Drosophila melanogaster.
The Quantitative PCR method was used for this purpose.
According to our results, Aspartame created statistically significant mtDNA damage. There was no
mtDNA damage in Saccharine+Cyclamate, Saccharine, Aceculfam K and Sucralose
application groups. These results indicate that the effects of aspartame in
human should carefully detect.

Kaynakça

  • AlSuhaibani, E.S. (2010). In vivo cytogenetic studies on aspartame. Comparative and Functional Genomics 2010 (605921): 1-4.
  • Bandyopadhyay, A., Ghoshai, S., Mukherjee, A. (2008). Genotoxicity testing of low-calorie sweeteners: aspartame, acesulfame-k, and saccharin. Drug and Chemical Toxicology 31: 447-457.
  • Belpoggi, F., Soffritti, M., Padovani, M., Esposti, D.D., Lauriola, M., Minardi, F. (2006). Results of long-term carcinogenicity bioassay on sprague-dawley rats exposed to asparta administered in feed. Annals of the New York Academy of Sciences 1076: 559-577.
  • Brusick, D., Grotz, V.L., Slesinski, R., Kruger, C.L., Hayes, A.W. (2010). The absence of genotoxicity of sucralose. Food and Chemical Toxicology 48: 3067-3072.
  • Demir, E., Turna, F., Aksakali S., Kaya, B., Marcos, R. (2014). Genotoxicity of different sweeteners in drosophila. Fresenius Environmental Bulletin 23(12): 3426-3432.
  • Gombos, K., Varjas, T., Orsós, Z., Polyák, E., Peredi, J., Varga, Z., Nowrasteh, G., Tettinger, A., Mucsi, G., Ember, I. (2007). The effect of aspartame administration on oncogene and suppressor gene expressions. In Vivo 21: 89-92.
  • Hoover, R.N., Strasser, P.H. (1980). Artificial sweeteners and human bladder cancer: preliminary results. The Lancet 315: 837-841.
  • Howe, G.R., Burch, J.D., Miller, A.B., Morrison, B., Gordon, P., Weldon, L., Chambers, L.W., Fodor, G., Winsor, G.M. (1977). Artificial sweeteners and human bladder cancer. The Lancet 2 (8038): 578-581.
  • Jeffrey, A.M., Williams, G.M. (2000). Lack of DNA-damaging activity of five non-nutritive sweeteners in the rat hepatocyte/DNA repais assay. Food and Chemical Toxicology 38: 335-338.
  • Kashanian, S., Khodaei, M.M., Kheirdoosh, F. (2013). In vitro DNA binding studies of aspartame, an artificial sweetener. Journal of Photochemistry and Photobiology B: Biology 120: 104-110.
  • Liang, F.Q., Godley, B.F. (2003). Oxidative stress-induced mitochondrial DNA damage in human retinal pigment epithelial cells: a possible mechanism for RPE aging and age-related macular degeneration. Experimental Eye Research 76 (4): 397-403.
  • Morrison, A.S., Buring, J.E. (1980). Artificial sweeteners and cancer of the lower urinary tract. The New England Journal of Medicine 302: 537-541.
  • Mourad, I.M. (2011). Effect of aspartame on some oxidative stres parameters in liver and kidney of rats. African Journal of Pharmacy and Pharmacology 5(6): 678-682.
  • Mutlu, A.G. (2012A). Measuring of DNA damage by quantitative PCR. In: Hernandez-Rodriguez P, Gomez APR (eds) Polymerase Chain Reaction. InTech, Rijeka, pp 283–292.
  • Mutlu, A.G. (2012 B). Increase in mitochondrial DNA copy number in response to ochratoxin a and methanol-induced mitochondrial DNA damage in drosophila. Bulletin of Environmental Contamination and Toxicology 89(6): 1129-1132.
  • Mutlu, A.G. (2013). The effects of a wheat germ rich diet on oxidative mtDNA damage, mtDNA copy number and antioxidant enzyme activities in aging Drosophila. ACTA Biologica Hungarica 64: 1-9.
  • Pettepher, C.C., LeDoux, S.P., Bohr, V.A., Wilson, G.L. (1991). Repair of alkali labile sites within the mitochondrial DNA of RINr 38 cells after exposure to nitrosourea streptozotocin. The Journal of Biological Chemistry 266 (5): 3113-3117.
  • Raben, A., Vasilaras, T.H., Muller, A.C., Astrup, A. (2002). Sucrose compared with artificial sweeteners: different effects on ad libitum food intake and body weight after 10 wk of supplementation in overweight subjects. The American Journal of Clinical Nutrition 76 (4): 721-729.
  • Rencüzoğulları, E., Tüylü, B.A., Topaktaş, M., İla, H.B., Kayraldız, A., Arslan, M., Diler, S.B. (2004). Genotoxicity of aspartame. Drug and Chemical Toxicology 27: 257-268.
  • Santos, J.H., Mandavilli, B.S., Van Houten, B. (2002). Measuring oxidative mtDNA damage and repair using QPCR. In: Copeland WC (ed) Mitochondrial DNA methods and protocols. Humana Press, Totawa, pp 159–176.
  • Sasaki, Y.F., Kawaguchi, S., Kamaya, A., Ohshita, M., Kabasawa, K., Iwama, K., Taniguchi, K., Tsuda, S. (2002). The comet assay with 8 mouse organs: results with 39 currently used food additives. Mutation Research 519: 103-119.
  • Shankar, P., Ahuja, S., Sriram, K. (2013). Non-nutritive sweeteners: review and update. Nutrition 29: 1293-1299.
  • 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 Perspevtives 114(3): 379-385.
  • Soffritti, M., Belpoggi, F., Tibaldi, E., Esposti, D.D., Lauriola, M. (2007). Life-span exposure to low doses of aspartame beginning during prenatal life increases cancer effects in rats. Environmental Health Perspectives 115 (9): 1293-1297.
  • Soffritti, M., Belpoggi, F., Manservigi, M., Tibaldi, E., Lauriol,a M., Falcioni, L., Bua, L. (2010). Aspartame administered in feed, beginning prenatally through life span, induces cancers of the liver and lung in male Swiss mice. American Journal of Industrial Medicine 53(12): 1197-1206.
  • Venkatraman, A., Landar, A., Davis, A.J., Chamlee, L., Sandersoni, T., Kim, H., Page, G., Pompilius, M., Ballinger, S., Darley-Usmar, V., Bailey, S.M. (2004). Modification of the mitochondrial proteome in response to the stress of ethanol-dependent hepatoxicity. J Biol Chem 279:22092–22101.
  • Wallace, D.C. (2002). Animal Models for Mitochondrial Disease. Mitochondrial DNA Methods and Protocols, Copeland WC, ed., Totawa, NJ, Humana Press Inc.,pp 3-39.
  • Weihrauch, M.R., Diehl, V. (2004). Artificial sweeteners-do they bear a carcinogenic risk?. Annals of Oncology 15: 1460-1465.
  • Whitehouse, C.R., Boullata, J., McCauley, L.A. (2008). The potential toxicity of artificial sweeteners. AAOHN Journal 56(6): 251-259.
  • Wynder, E.L., Stellman, S.D. (1980). Artificial sweetener use and bladder cancer: a case-control study. Science 207 (4436): 1214-1216.
  • Yakes, F.M., Van Houten, B. (1997). Mitochondrial DNA damage is more extensive and persists longer than nuclear DNA damage in human cells following oxidative stress. Proc Natl Acad Sci USA 94:514–519.
  • Yang, Q. (2010). Gain weight by “going diet?” artificial sweeteners and the neurobiology of sugar cracings. Yale Journal of Biology and Medicine 83: 101-108.
  • Yeşildal, F., Aydın, F.N., Deveci, S., Tekin, S., Aydın, I., Mammadov, R., Fermanlı, O., Avcu, F., Açıkel, C.H., Özgürtaş, T. (2015). Aspartame includes angiogenesis in vitro and in vivo models. Human & Experimental Toxicology 34(3): 260-265.

Drosophila’da Aspartam Tarafından Oluşturulan Mitokondrial DNA Hasarı

Yıl 2018, , 129 - 135, 25.04.2018
https://doi.org/10.29048/makufebed.377982

Öz

Yapay tatlandırıcılar çok çeşitli yiyecek, içecek,
ilaç ve hijyen ürünlerine eklenir. Bu ürünlerin herhangi birinin toksik
etkilerinin olması, toplumdaki birçok insan tarafından kullanıldığı için, halk
sağlığı açısından risk oluşturabilir. Bazı yapay tatlandırıcıların nüklear DNA
üzerindeki etkileri araştırılmış, ancak bu maddelerin mtDNA üzerindeki etkileri
hakkında herhangi bir çalışmaya literatürde rastlanmamıştır. Mitokondrial
genomdaki tüm bölgeler ifade edildiğinden, mtDNA’daki mutasyonlar, nDNA’daki
delesyonlardan potansiyel olarak daha önemli olabilir. Ayrıca, primer insan
kanserlerinde somatik mtDNA mutasyonları gittikçe artan bir şekilde
gözlenmektedir. Bu çalışmanın amacı, bazı yapay tatlandırıcıların mtDNA hasarı
ve kopya sayısına etkilerinin
Drosophila
melanogaster
’de saptanmasıdır. Bu amaçla kantitatif PCR yöntemi
kullanılmıştır. Sonuçlarımıza göre, Aspartam istatistiksel olarak anlamlı
derecede mtDNA hasarı oluşturmuştur. Sakkarin + Siklamat, Sakkarin, Asesulfam K
ve Sukraloz uygulama gruplarında ise mtDNA hasarı saptanmamıştır. Bu sonuçlar,
Aspartamın insanlar üzerinde yapabileceği olası etkilerinin dikkatle saptanması
gerektiğini göstermektedir.

Kaynakça

  • AlSuhaibani, E.S. (2010). In vivo cytogenetic studies on aspartame. Comparative and Functional Genomics 2010 (605921): 1-4.
  • Bandyopadhyay, A., Ghoshai, S., Mukherjee, A. (2008). Genotoxicity testing of low-calorie sweeteners: aspartame, acesulfame-k, and saccharin. Drug and Chemical Toxicology 31: 447-457.
  • Belpoggi, F., Soffritti, M., Padovani, M., Esposti, D.D., Lauriola, M., Minardi, F. (2006). Results of long-term carcinogenicity bioassay on sprague-dawley rats exposed to asparta administered in feed. Annals of the New York Academy of Sciences 1076: 559-577.
  • Brusick, D., Grotz, V.L., Slesinski, R., Kruger, C.L., Hayes, A.W. (2010). The absence of genotoxicity of sucralose. Food and Chemical Toxicology 48: 3067-3072.
  • Demir, E., Turna, F., Aksakali S., Kaya, B., Marcos, R. (2014). Genotoxicity of different sweeteners in drosophila. Fresenius Environmental Bulletin 23(12): 3426-3432.
  • Gombos, K., Varjas, T., Orsós, Z., Polyák, E., Peredi, J., Varga, Z., Nowrasteh, G., Tettinger, A., Mucsi, G., Ember, I. (2007). The effect of aspartame administration on oncogene and suppressor gene expressions. In Vivo 21: 89-92.
  • Hoover, R.N., Strasser, P.H. (1980). Artificial sweeteners and human bladder cancer: preliminary results. The Lancet 315: 837-841.
  • Howe, G.R., Burch, J.D., Miller, A.B., Morrison, B., Gordon, P., Weldon, L., Chambers, L.W., Fodor, G., Winsor, G.M. (1977). Artificial sweeteners and human bladder cancer. The Lancet 2 (8038): 578-581.
  • Jeffrey, A.M., Williams, G.M. (2000). Lack of DNA-damaging activity of five non-nutritive sweeteners in the rat hepatocyte/DNA repais assay. Food and Chemical Toxicology 38: 335-338.
  • Kashanian, S., Khodaei, M.M., Kheirdoosh, F. (2013). In vitro DNA binding studies of aspartame, an artificial sweetener. Journal of Photochemistry and Photobiology B: Biology 120: 104-110.
  • Liang, F.Q., Godley, B.F. (2003). Oxidative stress-induced mitochondrial DNA damage in human retinal pigment epithelial cells: a possible mechanism for RPE aging and age-related macular degeneration. Experimental Eye Research 76 (4): 397-403.
  • Morrison, A.S., Buring, J.E. (1980). Artificial sweeteners and cancer of the lower urinary tract. The New England Journal of Medicine 302: 537-541.
  • Mourad, I.M. (2011). Effect of aspartame on some oxidative stres parameters in liver and kidney of rats. African Journal of Pharmacy and Pharmacology 5(6): 678-682.
  • Mutlu, A.G. (2012A). Measuring of DNA damage by quantitative PCR. In: Hernandez-Rodriguez P, Gomez APR (eds) Polymerase Chain Reaction. InTech, Rijeka, pp 283–292.
  • Mutlu, A.G. (2012 B). Increase in mitochondrial DNA copy number in response to ochratoxin a and methanol-induced mitochondrial DNA damage in drosophila. Bulletin of Environmental Contamination and Toxicology 89(6): 1129-1132.
  • Mutlu, A.G. (2013). The effects of a wheat germ rich diet on oxidative mtDNA damage, mtDNA copy number and antioxidant enzyme activities in aging Drosophila. ACTA Biologica Hungarica 64: 1-9.
  • Pettepher, C.C., LeDoux, S.P., Bohr, V.A., Wilson, G.L. (1991). Repair of alkali labile sites within the mitochondrial DNA of RINr 38 cells after exposure to nitrosourea streptozotocin. The Journal of Biological Chemistry 266 (5): 3113-3117.
  • Raben, A., Vasilaras, T.H., Muller, A.C., Astrup, A. (2002). Sucrose compared with artificial sweeteners: different effects on ad libitum food intake and body weight after 10 wk of supplementation in overweight subjects. The American Journal of Clinical Nutrition 76 (4): 721-729.
  • Rencüzoğulları, E., Tüylü, B.A., Topaktaş, M., İla, H.B., Kayraldız, A., Arslan, M., Diler, S.B. (2004). Genotoxicity of aspartame. Drug and Chemical Toxicology 27: 257-268.
  • Santos, J.H., Mandavilli, B.S., Van Houten, B. (2002). Measuring oxidative mtDNA damage and repair using QPCR. In: Copeland WC (ed) Mitochondrial DNA methods and protocols. Humana Press, Totawa, pp 159–176.
  • Sasaki, Y.F., Kawaguchi, S., Kamaya, A., Ohshita, M., Kabasawa, K., Iwama, K., Taniguchi, K., Tsuda, S. (2002). The comet assay with 8 mouse organs: results with 39 currently used food additives. Mutation Research 519: 103-119.
  • Shankar, P., Ahuja, S., Sriram, K. (2013). Non-nutritive sweeteners: review and update. Nutrition 29: 1293-1299.
  • 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 Perspevtives 114(3): 379-385.
  • Soffritti, M., Belpoggi, F., Tibaldi, E., Esposti, D.D., Lauriola, M. (2007). Life-span exposure to low doses of aspartame beginning during prenatal life increases cancer effects in rats. Environmental Health Perspectives 115 (9): 1293-1297.
  • Soffritti, M., Belpoggi, F., Manservigi, M., Tibaldi, E., Lauriol,a M., Falcioni, L., Bua, L. (2010). Aspartame administered in feed, beginning prenatally through life span, induces cancers of the liver and lung in male Swiss mice. American Journal of Industrial Medicine 53(12): 1197-1206.
  • Venkatraman, A., Landar, A., Davis, A.J., Chamlee, L., Sandersoni, T., Kim, H., Page, G., Pompilius, M., Ballinger, S., Darley-Usmar, V., Bailey, S.M. (2004). Modification of the mitochondrial proteome in response to the stress of ethanol-dependent hepatoxicity. J Biol Chem 279:22092–22101.
  • Wallace, D.C. (2002). Animal Models for Mitochondrial Disease. Mitochondrial DNA Methods and Protocols, Copeland WC, ed., Totawa, NJ, Humana Press Inc.,pp 3-39.
  • Weihrauch, M.R., Diehl, V. (2004). Artificial sweeteners-do they bear a carcinogenic risk?. Annals of Oncology 15: 1460-1465.
  • Whitehouse, C.R., Boullata, J., McCauley, L.A. (2008). The potential toxicity of artificial sweeteners. AAOHN Journal 56(6): 251-259.
  • Wynder, E.L., Stellman, S.D. (1980). Artificial sweetener use and bladder cancer: a case-control study. Science 207 (4436): 1214-1216.
  • Yakes, F.M., Van Houten, B. (1997). Mitochondrial DNA damage is more extensive and persists longer than nuclear DNA damage in human cells following oxidative stress. Proc Natl Acad Sci USA 94:514–519.
  • Yang, Q. (2010). Gain weight by “going diet?” artificial sweeteners and the neurobiology of sugar cracings. Yale Journal of Biology and Medicine 83: 101-108.
  • Yeşildal, F., Aydın, F.N., Deveci, S., Tekin, S., Aydın, I., Mammadov, R., Fermanlı, O., Avcu, F., Açıkel, C.H., Özgürtaş, T. (2015). Aspartame includes angiogenesis in vitro and in vivo models. Human & Experimental Toxicology 34(3): 260-265.
Toplam 33 adet kaynakça vardır.

Ayrıntılar

Birincil Dil İngilizce
Konular Mühendislik
Bölüm Araştırma Makalesi
Yazarlar

Ayşe Gül Mutlu

Nesibe Kürklü Bu kişi benim

Yayımlanma Tarihi 25 Nisan 2018
Kabul Tarihi 11 Nisan 2018
Yayımlandığı Sayı Yıl 2018

Kaynak Göster

APA Mutlu, A. G., & Kürklü, N. (2018). Aspartame-Induced Mitochondrial DNA Damage in Drosophila. Mehmet Akif Ersoy Üniversitesi Fen Bilimleri Enstitüsü Dergisi, 9(2), 129-135. https://doi.org/10.29048/makufebed.377982