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Velum® Prime Kaynaklı DNA Hasarının İnsan Lenfositlerinde Değerlendirilmesi

Year 2023, Volume: 13 Issue: 5, 824 - 829, 30.09.2023
https://doi.org/10.16899/jcm.1345215

Abstract

Amaç: Fluopyram mitokondriyal kompleks II inhibitörü, suda çözünürlüğü düşük ve topraktaki yarılanma ömrü oldukça uzun bir pestisittir. Dolayısı ile insanlara ulaşması oldukça muhtemeldir. DNA hasarı üzerindeki etkisi insan lenfosit hücrelerinde comet metodu ile değerlendirilmiştir.
Gereç ve Yöntem: 8 gönüllüden histopak-1077 kullanılarak lenfositler elde edilmiştir. 0.05, 0.25 ve 1.00 mg/mL olmak üzere 3 dozda ve 1, 2 ve 4 saat fluopyram uygulaması yapılmıştır. Comet metodu uygulanmış ve hazırlanan preperatların floresan mikroskop altında fotoğrafları çekilmiştir. Preperat başına 50 hücre OpenComet programı ile değerlendirilmiş ve sonuçlar tek yönlü anova ile istatistiksel olarak değerlendirilmiştir.
Bulgular: 1.00 mg/mL 1 saat ve 0.05, 0.25, 1.00 mg/mL 2 ve 4 saat fluopyram uygulamaları internal kontrol gruplarına kıyasla DNA hasarında istatiksel olarak anlamlı artışa sebep olmuştur (p<0.05). Aynı uygulama süresine ve farklı doza sahip gruplar kendi arasında karşılaştırıldığında, 1 saat 1.00 mg/mL fluopyram uygulaması sonucunda DNA hasarında meydana gelen artış, 1 saat 0.05 mg/mL fluopyram uygulaması sonucunda meydana gelen artıştan daha yüksektir (p<0.05). Farklı uygulama süresine ve aynı doza sahip gruplar kendi arasında karşılaştırıldığında 4 saat 0.25 mg/mL fluopyram uygulaması sonucunda DNA hasarında meydana gelen artış, 1 saat 0.25 mg/mL fluopyram uygulaması sonucunda meydana gelen artıştan daha yüksektir (p<0.05).
Sonuç: Bu sonuçlara göre fluopyramın doz ve zaman bağımlı şekilde DNA hasarında artışa sebep olduğu tespit edilmiştir. Sonuçların in vivo olarak da araştırılması gerekmektedir.

Supporting Institution

Yok

Project Number

Yok

References

  • 1. Jackson SP, Bartek J. The DNA-damage response in human biology and disease. Nature. 2009;461(7267):1071-8.
  • 2. Elmore S. Apoptosis: A review of programmed cell death. Toxicol Pathol. 2007;35(4):495-516.
  • 3. Hakem R. DNA-damage repair; the good, the bad, and the ugly. EMBO J. 2008;27(4):589-605.
  • 4. Celik DA, Togay VA, Turel GY, Tuluceoglu EE, Kosar PA. DNA Damages of Widely Used Pesticides; A Comet Assay Report for Chlorothalonil and Glyphosate Potassium Salt. Fresenius Environ Bull. 2021;30(4 A):4170-6.
  • 5. Toğay VA, Yavuz Türel G, Aşcı Çelik D, Özgöçmen M, Evgen Tülüceoğlu E, Şen İ, et al. DNA damage effect of cyprodinil and thiacloprid in adult zebrafish gills. Environ Sci Pollut Res. 2021;28(12):14482-7.
  • 6. Yavuz Türel G, Toğay VA, Aşcı Çelik D. Genotoxicity of thiacloprid in zebrafish liver. Arch Environ Occup Health. 2022:78(3):152-157
  • 7. Çelik DA, Toğay VA. Rotenon’un İnsan Lenfositlerinde İn Vitro Genotoksisitesi. J Healt Sci SDU. 2022;13(3):448-55.
  • 8. Toğay VA, Çelik DA. Thiacloprid'in İnsan Lenfositlerinde DNA Hasarına Etkisi. Med J SDU. 2022;29(4):597-602.
  • 9. Sanborn M, Kerr KJ, Sanin LH, Cole DC, Bassil KL, Vakil C. Non-cancer health effects of pesticides: systematic review and implications for family doctors. Can Fam Physician. 2007;53(10):1712-20.
  • 10. Toğay VA. Pestisit Thiacloprid'in Parkinson Hastalığı ile Bağlantısının Araştırılması [DoktoraTezi]. Isparta: Süleyman Demirel Üniversitesi; 2021.
  • 11. Qian L, Cui F, Yang Y, Liu Y, Qi S, Wang C. Mechanisms of developmental toxicity in zebrafish embryos (Danio rerio) induced by boscalid. Sci Total Environ. 2018;634:478-87.
  • 12. Tinwell H, Rouquie D, Schorsch F, Geter D, Wason S, Bars R. Liver tumor formation in female rat induced by fluopyram is mediated by CAR/PXR nuclear receptor activation. Regul Toxicol Pharmacol. 2014;70(3):648-58.
  • 13. Li CJ, Yuan SF, Jiang F, Xie YF, Guo YH, Yu H, et al. Degradation of fluopyram in water under ozone enhanced microbubbles: Kinetics, degradation products, reaction mechanism, and toxicity evaluation. Chemosphere. 2020;258.
  • 14. Wu LT, Liu JN, Wang K, Pan S, Qi ZQ. Baseline sensitivity and resistance analysis of fluopyram against Botrytis cinerea from tomato in Liaoning Province, China. J of Phytopathol. 2023.
  • 15. Schleker ASS, Rist M, Matera C, Damijonaitis A, Collienne U, Matsuoka K, et al. Mode of action of fluopyram in plant-parasitic nematodes. Sci Rep. 2022;12(1):11954.
  • 16. Stucky T, Dahlin P. Fluopyram: Optimal Application Time Point and Planting Hole Treatment to Control Meloidogyne incognita. Agronomy. 2022;12(7):1576.
  • 17. Glei M, Schneider T, Schlörmann W. Comet assay: an essential tool in toxicological research. Arch Toxicol. 2016;90(10):2315-36.
  • 18. Liu Y, Zhang W, Wang Y, Liu H, Zhang S, Ji X, et al. Oxidative stress, intestinal damage, and cell apoptosis: Toxicity induced by fluopyram in Caenorhabditis elegans. Chemosphere. 2022;286:131830.
  • 19. OECD. Test No. 489: In Vivo Mammalian Alkaline Comet Assay. Paris: OECD Publishing; 2016.
  • 20. Gyori BM, Venkatachalam G, Thiagarajan P, Hsu D, Clement M-V. OpenComet: An automated tool for comet assay image analysis. Redox biol. 2014;2:457-65.
  • 21. IBMCorp. IBM SPSS Statistics for Windows, Version 29.0. Armonk, NY: IBM Corp.; 2022.
  • 22. Hua X, Liu N, Zhou S, Zhang L, Yin H, Wang G, et al. Design, Synthesis, and Biological Activity of Novel Aromatic Amide Derivatives Containing Sulfide and Sulfone Substructures. Engineering. 2020;6(5):553-9.
  • 23. Nanusha MY, Frokjaer EE, Liigand J, Christensen MR, Hansen HR, Hansen M. Unravelling the occurrence of trace contaminants in surface waters using semi-quantitative suspected non-target screening analyses. Environ Pollut. 2022;315.
  • 24. Penagos-Tabares F, Sulyok M, Faas J, Krska R, Khiaosa-ard R, Zebeli Q. Residues of pesticides and veterinary drugs in diets of dairy cattle from conventional and organic farms in Austria. Environ Pollut. 2023;316.
  • 25. Yu Y, Cui YX, Niedernhofer LJ, Wang YS. Occurrence, Biological Consequences, and Human Health Relevance of Oxidative Stress-Induced DNA Damage. Chem Res Toxicol. 2016;29(12):2008-39.
  • 26. Aktaş C, Çelik A, Yalın S, Güler G. The Investigation of Genotoxicity and Oxidative Stress Potential of Luna Experience SC 400 Fungucide in Rat Liver and Blood Tissues. J Public Health Dis Prev. 2018;1(1):101.
  • 27. Celik A, Guler G, Aktas C, Yalin S. Genotoxic action of Luna Experience-SC 400 fungicide on rat bone marrow. Biomarkers. 2019;24(7):720-5.
  • 28. Cayir A, Coskun M, Coskun M. Micronuclei, Nucleoplasmic Bridges, and Nuclear Buds Induced in Human Lymphocytes by the Fungicide Signum and Its Active Ingredients (Boscalid and Pyraclostrobin). Environ Toxicol. 2014;29(7):723-32.
  • 29. Graillot V, Tomasetig F, Cravedi J-P, Audebert M. Evidence of the in vitro genotoxicity of methyl-pyrazole pesticides in human cells. Mutat Res Genet Toxicol Environ Mutagen. 2012;748(1-2):8-16.
  • 30. He FL, Wan JQ, Li XX, Chu SS, Sun N, Liu RT. Toxic effects of benzovindiflupyr, a new SDHI-type fungicide on earthworms (Eisenia fetida). Environ Sci Pollut Res. 2021;28(44):62782-95.
  • 31. Akyil D, Ozkara A, Erdogmus SF, Eren Y, Konuk M, Saglam E. Evaluation of cytotoxic and genotoxic effects of Benodanil by using Allium and Micronucleus assays. Drug Chem Toxicol. 2016;39(1):35-40.
  • 32. Ren B, Zhao TT, Li YH, Liang HL, Zhao YX, Chen HY, et al. Enantioselective bioaccumulation and toxicity of the novel chiral antifungal agrochemical penthiopyrad in zebrafish (Danio rerio). Ecotoxicol Environ Saf. 2021;228.
  • 33. Teng MM, Zhou YM, Song M, Dong K, Chen XG, Wang CJ, et al. Chronic Toxic Effects of Flutolanil on the Liver of Zebrafish (Danio rerio). Chem Res Toxicol. 2019;32(6):995-1001.
  • 34. EFSA (European Food Safety Authority), et al. Modification of the existing maximum residue levels and setting of import tolerances for fluopyram in various crops. EFSA Journal. 2023;21(6):e08036.
  • 35. Ren S, Zhang Y, Zhang S, Lu H, et al. Residue behavior and dietary risk assessment of fluopyram in cowpea and determination in nine foodstuffs. Front Environ Sci. 2023;11:20.

Assessment of DNA Damage Induced by Velum® Prime in Human Lymphocytes

Year 2023, Volume: 13 Issue: 5, 824 - 829, 30.09.2023
https://doi.org/10.16899/jcm.1345215

Abstract

Aim: Fluopyram is a mitochondrial complex II inhibitor with low water solubility and a relatively long half-life in soil. So it may also be dangerous for humans. The effect of fluopyram on DNA damage was evaluated in human lymphocytes using the comet assay.
Materials and Methods: Lymphocytes of eight volunteers were isolated using histopaque-1077. Fluopyram was administered at doses of 0.05, 0.25, and 1.00 mg/mL for 1, 2, and 4 h. The comet assay was applied, and photographs of the slides were taken under a fluorescence microscope. 50 cells per slide were analyzed using the OpenComet software. The obtained results were statistically evaluated using one-way ANOVA.
Results: Fluopyram treatments at 1.00 mg/mL for 1 h and 0.05, 0.25, and 1.00 mg/mL for 2 and 4 h resulted in a statistically significant increase in DNA damage compared to the internal control groups (p<0.05). When comparing groups with the same treatment time but different doses, the increase in DNA damage observed after a 1-h treatment of 1.00 mg/mL fluopyram was higher than the increase observed after a 1-h treatment of 0.05 mg/mL fluopyram (p<0.05). When comparing groups with different treatment times but the same dose, the increase in DNA damage after a 4-h treatment of 0.25 mg/mL fluopyram was higher than the increase observed after a 1-h treatment of 0.25 mg/mL fluopyram (p<0.05).
Conclusions: The results suggest that fluopyram causes an increase in DNA damage in a dose- and time-dependent manner. It is essential to investigate these findings in vivo as well.

Project Number

Yok

References

  • 1. Jackson SP, Bartek J. The DNA-damage response in human biology and disease. Nature. 2009;461(7267):1071-8.
  • 2. Elmore S. Apoptosis: A review of programmed cell death. Toxicol Pathol. 2007;35(4):495-516.
  • 3. Hakem R. DNA-damage repair; the good, the bad, and the ugly. EMBO J. 2008;27(4):589-605.
  • 4. Celik DA, Togay VA, Turel GY, Tuluceoglu EE, Kosar PA. DNA Damages of Widely Used Pesticides; A Comet Assay Report for Chlorothalonil and Glyphosate Potassium Salt. Fresenius Environ Bull. 2021;30(4 A):4170-6.
  • 5. Toğay VA, Yavuz Türel G, Aşcı Çelik D, Özgöçmen M, Evgen Tülüceoğlu E, Şen İ, et al. DNA damage effect of cyprodinil and thiacloprid in adult zebrafish gills. Environ Sci Pollut Res. 2021;28(12):14482-7.
  • 6. Yavuz Türel G, Toğay VA, Aşcı Çelik D. Genotoxicity of thiacloprid in zebrafish liver. Arch Environ Occup Health. 2022:78(3):152-157
  • 7. Çelik DA, Toğay VA. Rotenon’un İnsan Lenfositlerinde İn Vitro Genotoksisitesi. J Healt Sci SDU. 2022;13(3):448-55.
  • 8. Toğay VA, Çelik DA. Thiacloprid'in İnsan Lenfositlerinde DNA Hasarına Etkisi. Med J SDU. 2022;29(4):597-602.
  • 9. Sanborn M, Kerr KJ, Sanin LH, Cole DC, Bassil KL, Vakil C. Non-cancer health effects of pesticides: systematic review and implications for family doctors. Can Fam Physician. 2007;53(10):1712-20.
  • 10. Toğay VA. Pestisit Thiacloprid'in Parkinson Hastalığı ile Bağlantısının Araştırılması [DoktoraTezi]. Isparta: Süleyman Demirel Üniversitesi; 2021.
  • 11. Qian L, Cui F, Yang Y, Liu Y, Qi S, Wang C. Mechanisms of developmental toxicity in zebrafish embryos (Danio rerio) induced by boscalid. Sci Total Environ. 2018;634:478-87.
  • 12. Tinwell H, Rouquie D, Schorsch F, Geter D, Wason S, Bars R. Liver tumor formation in female rat induced by fluopyram is mediated by CAR/PXR nuclear receptor activation. Regul Toxicol Pharmacol. 2014;70(3):648-58.
  • 13. Li CJ, Yuan SF, Jiang F, Xie YF, Guo YH, Yu H, et al. Degradation of fluopyram in water under ozone enhanced microbubbles: Kinetics, degradation products, reaction mechanism, and toxicity evaluation. Chemosphere. 2020;258.
  • 14. Wu LT, Liu JN, Wang K, Pan S, Qi ZQ. Baseline sensitivity and resistance analysis of fluopyram against Botrytis cinerea from tomato in Liaoning Province, China. J of Phytopathol. 2023.
  • 15. Schleker ASS, Rist M, Matera C, Damijonaitis A, Collienne U, Matsuoka K, et al. Mode of action of fluopyram in plant-parasitic nematodes. Sci Rep. 2022;12(1):11954.
  • 16. Stucky T, Dahlin P. Fluopyram: Optimal Application Time Point and Planting Hole Treatment to Control Meloidogyne incognita. Agronomy. 2022;12(7):1576.
  • 17. Glei M, Schneider T, Schlörmann W. Comet assay: an essential tool in toxicological research. Arch Toxicol. 2016;90(10):2315-36.
  • 18. Liu Y, Zhang W, Wang Y, Liu H, Zhang S, Ji X, et al. Oxidative stress, intestinal damage, and cell apoptosis: Toxicity induced by fluopyram in Caenorhabditis elegans. Chemosphere. 2022;286:131830.
  • 19. OECD. Test No. 489: In Vivo Mammalian Alkaline Comet Assay. Paris: OECD Publishing; 2016.
  • 20. Gyori BM, Venkatachalam G, Thiagarajan P, Hsu D, Clement M-V. OpenComet: An automated tool for comet assay image analysis. Redox biol. 2014;2:457-65.
  • 21. IBMCorp. IBM SPSS Statistics for Windows, Version 29.0. Armonk, NY: IBM Corp.; 2022.
  • 22. Hua X, Liu N, Zhou S, Zhang L, Yin H, Wang G, et al. Design, Synthesis, and Biological Activity of Novel Aromatic Amide Derivatives Containing Sulfide and Sulfone Substructures. Engineering. 2020;6(5):553-9.
  • 23. Nanusha MY, Frokjaer EE, Liigand J, Christensen MR, Hansen HR, Hansen M. Unravelling the occurrence of trace contaminants in surface waters using semi-quantitative suspected non-target screening analyses. Environ Pollut. 2022;315.
  • 24. Penagos-Tabares F, Sulyok M, Faas J, Krska R, Khiaosa-ard R, Zebeli Q. Residues of pesticides and veterinary drugs in diets of dairy cattle from conventional and organic farms in Austria. Environ Pollut. 2023;316.
  • 25. Yu Y, Cui YX, Niedernhofer LJ, Wang YS. Occurrence, Biological Consequences, and Human Health Relevance of Oxidative Stress-Induced DNA Damage. Chem Res Toxicol. 2016;29(12):2008-39.
  • 26. Aktaş C, Çelik A, Yalın S, Güler G. The Investigation of Genotoxicity and Oxidative Stress Potential of Luna Experience SC 400 Fungucide in Rat Liver and Blood Tissues. J Public Health Dis Prev. 2018;1(1):101.
  • 27. Celik A, Guler G, Aktas C, Yalin S. Genotoxic action of Luna Experience-SC 400 fungicide on rat bone marrow. Biomarkers. 2019;24(7):720-5.
  • 28. Cayir A, Coskun M, Coskun M. Micronuclei, Nucleoplasmic Bridges, and Nuclear Buds Induced in Human Lymphocytes by the Fungicide Signum and Its Active Ingredients (Boscalid and Pyraclostrobin). Environ Toxicol. 2014;29(7):723-32.
  • 29. Graillot V, Tomasetig F, Cravedi J-P, Audebert M. Evidence of the in vitro genotoxicity of methyl-pyrazole pesticides in human cells. Mutat Res Genet Toxicol Environ Mutagen. 2012;748(1-2):8-16.
  • 30. He FL, Wan JQ, Li XX, Chu SS, Sun N, Liu RT. Toxic effects of benzovindiflupyr, a new SDHI-type fungicide on earthworms (Eisenia fetida). Environ Sci Pollut Res. 2021;28(44):62782-95.
  • 31. Akyil D, Ozkara A, Erdogmus SF, Eren Y, Konuk M, Saglam E. Evaluation of cytotoxic and genotoxic effects of Benodanil by using Allium and Micronucleus assays. Drug Chem Toxicol. 2016;39(1):35-40.
  • 32. Ren B, Zhao TT, Li YH, Liang HL, Zhao YX, Chen HY, et al. Enantioselective bioaccumulation and toxicity of the novel chiral antifungal agrochemical penthiopyrad in zebrafish (Danio rerio). Ecotoxicol Environ Saf. 2021;228.
  • 33. Teng MM, Zhou YM, Song M, Dong K, Chen XG, Wang CJ, et al. Chronic Toxic Effects of Flutolanil on the Liver of Zebrafish (Danio rerio). Chem Res Toxicol. 2019;32(6):995-1001.
  • 34. EFSA (European Food Safety Authority), et al. Modification of the existing maximum residue levels and setting of import tolerances for fluopyram in various crops. EFSA Journal. 2023;21(6):e08036.
  • 35. Ren S, Zhang Y, Zhang S, Lu H, et al. Residue behavior and dietary risk assessment of fluopyram in cowpea and determination in nine foodstuffs. Front Environ Sci. 2023;11:20.
There are 35 citations in total.

Details

Primary Language English
Subjects Medical Genetics (Excl. Cancer Genetics)
Journal Section Original Research
Authors

Vehbi Atahan Toğay 0000-0003-4722-3845

Dilek Aşcı Çelik 0000-0002-2914-4695

Project Number Yok
Publication Date September 30, 2023
Acceptance Date September 13, 2023
Published in Issue Year 2023 Volume: 13 Issue: 5

Cite

AMA Toğay VA, Aşcı Çelik D. Assessment of DNA Damage Induced by Velum® Prime in Human Lymphocytes. J Contemp Med. September 2023;13(5):824-829. doi:10.16899/jcm.1345215