Merve ARAS, Özlem YAYINTAŞ, Sibel OYMAK YALÇIN

Pestisitlerin DNA affinite düzeylerinin incelenmesi: docking analiz sonuçlari

Amaç: Son yıllarda yapılan çalışmalara göre pestisitler kanser, Parkinson hastalığı, Alzheimer hastalığı, üreme sistemi bozuklukları ve doğum defektleri gelişimine yol açabilmektedir. Bu çalışmanın amacı Alfa-sipermetrin, Malathion, Quinclorac, Roundup (Glyphosate) bitki koruma ürünlerinin DNA afinite düzeylerini incelemek ve literatur eşliğinde tartışmaktır. Yöntem: Ligand ve reseptör arasındaki docking sonuçları Hex 8.0.0 yazılımı kullanılarak tespit edildi. Reseptör ve ligandın docking için hazırlanması UCSF Chimera 1.15 yazılımı ile yapıldı. Docking görselleştirmeleri BIOVIA Discovery Studio ve PyMol yazılımları ile yapıldı. Pestisitlerin DNA ile olan etkileşim görüntüleri BIOVIA Discovery Studio yazılımı ile tespit edilirken, DNA’ya bağlanma görüntüleri PyMol yazılımı ile tespit edildi. Bulgular: Çalışmamızda Çanakkale bölgesinde sık kullanılan bitki koruma ürünlerinin docking analiz sonuçlarına göre DNA molekülüne olan affinite düzeyleri sırasıyla Alpha Cypermethrin>Malathion>Quinclorac>Roundup/Glyphosate şeklinde tespit edildi. DNA ile en yüksek etkileşim içinde olan pestisit Alpha Cypermethrin (-248.24 KJ mol-1) ve en düşük bağlanma enerjili ise Roundup (-161.54 KJ mol-1) olarak tespit edildi. Sonuç: Alfa-sipermetrin literatürle de uyumlu olarak toksisistesi ve gen hasarı oluşturma potansiyeli en yüksek moleküldür. Ürün çeşitliliği göz önüne alındığında hem tekli hem de çoklu bitki koruma ürünleri kullanımına dikkat edilmesi gerekmektedir. Bu molekül kullanımı sırasında alternatif olarak yerine geçebilecek daha düşük DNA affinitesi ve toksisitesi olan bitki koruma ürünleri tercih edilebilir.

Anahtar Kelimeler:

moleküler docking, alfa-sipermetrin, malathion, quinclorac, roundup(glyphosate)

Investigation of DNA affinity levels of pesticides: docking analysis results

Objective: According to studies conducted in recent years, pesticides can lead to the development of cancer, Parkinson's disease, Alzheimer's disease, reproductive system disorders, and birth defects. The aim of this study is to examine the DNA affinity levels of Alpha-cypermethrin, Malathion, Quinclorac, and Roundup (Glyphosate) plant protection products and to discuss them in the light of the literature. Methods: Docking results between ligand and receptor were detected using Hex 8.0.0 software. Preparation of the receptor and ligand for docking was done with UCSF Chimera 1.15 software. Docking visualizations were made with BIOVIA Discovery Studio and PyMol software. While the interaction images of pesticides with DNA were detected with BIOVIA Discovery Studio software, DNA binding images were detected with PyMol software. Results: In our study, the affinity levels of the plant protection products frequently used in the Çanakkale region were determined as Alpha Cypermethrin>Malathion>Quinclorac>Roundup /Glyphosate, respectively, according to the results of the docking analysis. The pesticide with the highest interaction with DNA was Alpha Cypermethrin (-248.24 KJ mol-1) and the lowest binding energy was Roundup (-161.54 KJ mol-1). Conclusion: In line with the literature, alpha-cypermethrin is the molecule with the highest toxicity and gene damage potential. Considering the variety of products, it is necessary to pay attention to the use of both single and multiple plant protection products. During the use of this molecule, plant protection products with lower DNA affinity and toxicity can be preferred as an alternative.

Keywords:

molecular docking, alpha cypermethrin, malathion quinclorac, roundup (glyphosate), : moleküler docking, alfa-sipermetrin, moleküler docking,

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1. FAO. 2017. The future of food and agriculture – Trends and challenges. Rome. ISBN 978-92-5-109551-5.
2. CODEX ALIMENTARIUS, International Food Standards. http://www.fao.org/fao-who-codexalimentarius/standards/pestres/en/. Accessed on May 11, 2022.
3. Abdelfattah EA, El-Bassiony GM. Impact of malathion toxicity on the oxidative stress parameters of the black soldier fly Hermetia illucens (Linnaeus, 1758) (Diptera: Stratiomyidae). Sci Rep 2022;12(1):1–12.
4. Starks SE, Gerr F, Kamel F, Lynch CF, Jones MP, Alavanja MC, et al. Central nervous system function and organophosphate insecticide use among pesticide applicators in the Agricultural Health Study. NIH Public Access 2012;34(1):168–76.
5. Curl CL, Spivak M, Phinney R, Montrose L. Synthetic Pesticides and Health in Vulnerable Populations: Agricultural Workers. Curr Environ Health Rep 2020;7(1):13-29.
6. Beyond pesticides. Pesticide-Induced Diseases: Cancer. https://www.beyondpesticides.org/resources/pesticide-induced-diseases-database/cancer. Accessed on May 08, 2022.
7. Moshou H, Karakitsou A, Yfanti F, et al. Assessment of genetic effects and pesticide exposure of farmers in NW Greece. Environ Res 2020; 186:109558.
8. Latifovic L, Freeman LEB, Spinelli JJ, et al. Pesticide use and risk of Hodgkin lymphoma: results from the North American Pooled Project (NAPP). Cancer Causes Control 2020 Jun;31(6):583-599.
9. Blair A, Freeman LB. Epidemiologic studies in agricultural populations: observations and future directions. J Agromedicine 2009;14(2):125–131.
10. Blair A, Zahm SH. Cancer among farmers. Occup Med 1991;6(3):335–354
11. Blair A, Zahm SH, Pearce NE, Heineman EF, Fraumeni JF Jr. Clues to cancer etiology from studies of farmers. Scand J Work Environ Health 1992;18(4):209–215
12. Kachuri L, Harris MA, MacLeod JS, Tjepkema M, Peters PA, Demers PA. Cancer risks in a population-based study of 70,570 agricultural workers: results from the Canadian census health and Environment cohort (CanCHEC). BMC Cancer 2012;17(1):343.
13. Starks SE, Hoppin JA, Kamel F, et al. Peripheral nervous system function and organophosphate pesticide use among licensed pesticide applicators in the Agricultural Health Study. Environ Health Perspect 2012; 120(4):515–520.
14. Alavanja MC, Hoppin JA, Kamel F. Health effects of chronic pesticide exposure: cancer and neurotoxicity. Annu Rev Public Health 2004; 25:155–197.
15. Androutsopoulos VP, Hernandez AF, Liesivuori J, Tsatsakis AM. A mechanistic overview of health-associated effects of low levels of organochlorine and organophosphorus pesticides. Toxicology 2013; 307:89–94.
16. Alavanja MC, Ross MK, Bonner MR. Increased cancer burden among pesticide applicators and others due to pesticide exposure. CA Cancer J Clin 2013;63(2):120–142.
17. George J, Shukla Y. Pesticides and cancer: insights into toxicoproteomic-based findings. J Proteomics 2011;74(12):2713–2722.
18. Parron T, Requena M, Hernandez AF, Alarcon R. Environmental exposure to pesticides and cancer risk in multiple human organ systems. Toxicol Lett 2014;230(2):157–165.
19. Hreljac I, Zajc I, Lah T, Filipic M. Effects of model organophosphorus pesticides on DNA damage and proliferation of HepG2 cells. Environ Mol Mutagen 2008;49(5):360–367.
20. Hernandez AF, Amparo Gomez M, Perez V, et al. Influence of exposure to pesticides on serum components and enzyme activities of cytotoxicity among intensive agriculture farmers. Environ Res 2006;102(1):70–76.
21. Lu XT, Ma Y, Wang C, et al. Cytotoxicity and DNA damage of five organophosphorus pesticides mediated by oxidative stress in PC12 cells and protection by vitamin E. J Environ Sci Health B 2012;47(5):445–454.
22. Mesnage R, Defarge N, Spiroux de Vendomois J, Seralini GE. Major pesticides are more toxic to human cells than their declared active principles. Biomed Res Int 2014:179691.
23. Ojha A, Yaduvanshi SK, Pant SC, Lomash V, Srivastava N. Evaluation of DNA damage and cytotoxicity induced by three commonly used organophosphate pesticides individually and in mixture, in rat tissues. Environ Toxicol 2013;28(10):543–552.
24. Sultana Shaik A, Shaik AP, Jamil K, Alsaeed AH. Evaluation of cytotoxicity and genotoxicity of pesticide mixtures on lymphocytes. Toxicol Mech Methods 2016;26(8):588–594.
25. Zhang Q, Yu S, Chen X, et al. Stereoisomeric selectivity in the endocrine-disrupting potential of cypermethrin using in vitro, in vivo, and in silico assays. J Hazard Mater 2021; 414:125389.
26. Yao G, Gao J, Zhang C, et al. Enantioselective degradation of the chiral alpha-cypermethrin and detection of its metabolites in five plants. Environ Sci Pollut Res Int 2019 Jan;26(2):1558-1564.
27. El Okda ES, Abdel-Hamid MA, Hamdy AM. Immunological and genotoxic effects of occupational exposure to α-cypermethrin pesticide. Int J Occup Med Environ Health 2017;30(4):603-615.
28. Ding Z, Shen JY, Hong JW, et al. Inhibitory Effects of Cypermethrin on Interactions of the Androgen Receptor with Coactivators ARA70 and ARA55. Biomed Environ Sci 2020;33(3):158-164.
29. Wang Q, Xu LF, Zhou JL, et al. Antagonism effects of cypermethrin on interleukin-6-induced androgen receptor activation. Environ Toxicol Pharmacol 2015;40(1):172-4.
30. Chrustek A, Hołyńska-Iwan I, Dziembowska I, et al. Current Research on the Safety of Pyrethroids Used as Insecticides. Medicina (Kaunas) 2018;54(4):61.
31. Cunha EO, Reis AD, Macedo MB, Machado MS, Dallegrave E. Ototoxicity of cypermethrin in Wistar rats. Braz J Otorhinolaryngol 2020;86(5):587-592.
32. Katragadda V, Adem M, Mohammad RA, Sri Bhasyam S, Battini K. Testosterone recuperates deteriorated male fertility in cypermethrin intoxicated rats. Toxicol Res 2020;37(1):125-134.
33. EPA. Reregistration Eligibility Decision for Malathion (Revised) Wayback Machine on 30 April 2017., US EPA, May 2009.
34. "Malathion Technical Fact Sheet". Archived from the original on 11 May 2015. Accessed on April 14, 2018.
35. Xu W, Di C, Zhou S, et al. Rice transcriptome analysis to identify possible herbicide quinclorac detoxification genes. Front Genet 2015; 6:306.
36. Van Bruggen AHC, He MM, Shin K, et al. Environmental and health effects of the herbicide glyphosate. Sci Total Environ 2018;616-617:255-268.
37. Johnson RAB, Hann K, Leno A, et al. Pesticide Importation in Sierra Leone, 2010-2021: Implications for Food Production and Antimicrobial Resistance. Int J Environ Res Public Health 2022;19(8):4792.
38. Giacometti F., Shirzad-Aski H., Ferreira S. Antimicrobials and Food-Related Stresses as Selective Factors for Antibiotic Resistance along the Farm to Fork Continuum. Antibiotics 2021; 10:671.
39. Liao H., Li X., Yang Q., et al. Herbicide Selection Promotes Antibiotic Resistance in Soil Microbiomes. Mol. Biol. Evol 2021; 38:2337–2350.
40. Lerro CC, Koutros S, Andreotti G, et al. Organophosphate insecticide use and cancer incidence among spouses of pesticide applicators in the Agricultural Health Study. Occup Environ Med 2015;72(10):736–744.