The study of primary DNA damage in the bone marrow of mice under the combined action of pesticides

Cover Page

Cite item

Full Text

Abstract

Introduction. The study of the potential negative effects of combinations of several pesticide active ingredients is an important and understudied area of ​​toxicological and hygienic research. The initial phase of the genotoxicant action on the genetic structures in cells is the primary DNA damage, the identification of which makes it possible to assess the early stages of the genotoxic effect of xenobiotics and their mixtures. The DNA comet assay is widely used for these purposes.

The aim of the research is to assess the primary DNA damage under the combined action of pesticides.

Materials and methods. To assess DNA damage the experiments on CD-1 mice of both sexes were performed using alkaline comet analysis. The concentration of active products reacting with thiobarbituric acid (TBA) in the blood serum of white outbred rats was assessed as a marker of lipid peroxidation.

Results. It was found that mixtures of 2,4-D-acid + glyphosate and thiram + carbendazim did not cause the formation of breaks and alkali-labile sites in the DNA of mice bone marrow cells. Exposure to the combination of the technical grade active ingredients captan and fludioxonil induced the breaks and alkali-labile sites in the DNA of animal bone marrow cells. The comparison of the genotoxicity assessment results obtained by the comet assay and results of analysis of the TBA-active product concentrations in the rat blood serum suggests that the observed primary DNA damage upon exposure to the captan and fludioxonil combination can be mediated by the induction of lipid peroxidation and subsequent interaction of the resulting products with nucleic acids.

Conclusion. The results indicate that some pesticides in combination can damage hereditary material in mammalian cells. Therefore, in order to ensure the safe use of pesticides for public health it is necessary to take into account the data on the genotoxicity not only of individual pesticide technical grade active ingredients but also their combinations.

About the authors

Nataliya S. Averianova

Federal Budgetary Establishment of Science “ F.F. Erisman Federal Scientific Center of Hygiene” of the Federal Service for Surveillance on Consumer Rights Protection and Human Wellbeing

Author for correspondence.
Email: averianovans@fferisman.ru
ORCID iD: 0000-0002-2973-8776

PhD, senior researcher of the department of genetic toxicology, FBES “F.F. Erisman Federal Scientific Center of Hygiene” of the Federal Service for Surveillance on Consumer Rights Protection and Human Wellbeing, 141014, Mytishchi, Moscow region, Russia.

e-mail: averianovans@fferisman.ru

Russian Federation

Liliya A. Kara

Federal Budgetary Establishment of Science “ F.F. Erisman Federal Scientific Center of Hygiene” of the Federal Service for Surveillance on Consumer Rights Protection and Human Wellbeing

Email: karala@fferisman.ru
ORCID iD: 0000-0002-4635-2496

Младший научный сотрудник отдела генетической токсикологии ФБУН «ФНЦГ им. Ф.Ф. Эрисмана» Роспотребнадзора, г. Мытищи Московской области.

e-mail: karala@fferisman.ru

Russian Federation

Olga V. Egorova

Federal Budgetary Establishment of Science “ F.F. Erisman Federal Scientific Center of Hygiene” of the Federal Service for Surveillance on Consumer Rights Protection and Human Wellbeing

Email: egorovaov@fferisman.ru
ORCID iD: 0000-0003-4748-8771

Кандидат биологических наук, старший научный сотрудник отдела генетической токсикологии ФБУН «ФНЦГ им. Ф.Ф. Эрисмана» Роспотребнадзора, г. Мытищи Московской области.

e-mail: egorovaov@fferisman.ru 

Russian Federation

Nataliya A. Ilyushina

Federal Budgetary Establishment of Science “ F.F. Erisman Federal Scientific Center of Hygiene” of the Federal Service for Surveillance on Consumer Rights Protection and Human Wellbeing

Email: iliushinana@fferisman.ru
ORCID iD: 0000-0001-9122-9465

Доктор биологических наук, заведующая отделом генетической токсикологии ФБУН «ФНЦГ им. Ф.Ф. Эрисмана» Роспотребнадзора, г. Мытищи Московской области.

e-mail: iliushinana@fferisman.ru

Russian Federation

References

  1. Azarov O.I., Coj V.G., Chekmarev P.A., Jushkov A.Ju. Chemical plant protection products: the world and Russian market. [Himicheskie sredstva zashchity rastenij mirovoj i rossijskij rynok] Moscow: OOO «Leoving»; 2018, 112. (in Russian)
  2. Bychkov K.V. Equation with two unknowns. Product quality control [Kontrol kachestva produkcii]. 2014; 11: 35-41. (in Russian)
  3. Shubina A.G., Sinyutina S.E., Shubin R.A. The content of pesticides in grain of cereals and arable soils of a number of districts of the Tambov region. Vestnik TGTU. 2009; 15 (1): 208-11. (in Russian)
  4. The 2016 European Union report on pesticide residues in food. European Food Safety Authority. 2018; 16 (7): 1-139. https://doi.org/10.2903/j.efsa.2018.5348
  5. Vodanyuk S. How many pesticides remain in vegetables and fruits? Available at: https://rosorganic.ru/news/how-much-pesticide-remains-in-veget.html. Accessed 20.04.2021. (In Russian)
  6. Committee on Toxicity of Chemicals in Food, Consumer Products and the Environment. Risk Assessment of Mixtures of Pesticides and Similar Substances. Available at: https://cot.food.gov.uk/sites/default/files/cot/reportindexed.pdf Accessed 20.04.2021.
  7. González M., Soloneski S., Reigosa M.A., Larramendy M.L. Genotoxicity of the herbicide 2,4-dichlorophenoxyacetic and a commercial formulation, 2,4-dichlorophenoxyacetic acid dimethylamine salt. I. Evaluation of DNA damage and cytogenetic endpoints in Chinese Hamster ovary (CHO) cells. Toxicology in vitro. 2005; 19(2): 289-97. https://doi.org/10.1016/j.tiv.2004.10.004
  8. Rai B., Mercurio S.D. Environmentally relevant exposures of male mice to carbendazim and thiram cause persistent genotoxicity in male mice. Environmental Science and Pollution Research. 2020; 27: 10629-41. https://doi.org/10.1007/s11356-019-07088-5
  9. Rahman M.F., Mahboob M., Danadevi K., Saleha B.B., Grover P. Assessment of genotoxic effects of chloropyriphos and acephate by the comet assay in mice leucocytes. Mutation research. 2002; 516 (1-2): 139-47. https://doi.org/10.1016/s1383-5718(02)00033-5
  10. Sarrif A.M., Bentley K.S., Fu L.J., O’Neil R.M., Reynolds V.L., Stahl R.G. Evaluation of benomyl and carbendazim in the vivo aneuploidy/micronucleus assay in BDF1 mouse bone marrow. Mutation Research. 1994; 310 (1): 143-9. https://doi.org/10.1016/0027-5107(94)90018-3
  11. Ilyushina N.A. Cytogenetic effects of carbendazim on mouse bone marrow cells. Genetica. 2020; 56 (10): 1193-202. https://doi.org/10.1134/S 1022795420090094 (in Russian)
  12. McCarroll N.E., Protzel A., Ioannou Y., Frank S.H.F., Jackson M.A., Waters M.D. et al. A survey of EPA/OPP and open literature on selected pesticide chemicals: III. Mutagenicity and carcinogenicity of benomyl and carbendazim. Mutation Research. 2002; 512 (1): 1-35. https://doi.org/10.1016/s1383-5742(02)00026-1
  13. Arce G.T., Gordon E.B, Cohen S.M., Singh P. Genetic toxicology of folpet and captan. Critical Reviews in Toxicology. 2010; 40 (6): 546-74. https://doi.org/10.3109/10408444.2010.481663
  14. The European Chemicals Agency. Thiram. Registration dossier. Available at: https://echa.europa.eu/registration-dossier/-/registered-dossier/11311/4/21 Accessed 20.04.2021.
  15. European Food Safety Authority. Peer review of the pesticide risk assessment of the active substance thiram. Available at: https://efsa.onlinelibrary.wiley.com/doi/10.2903/j.efsa.2017.4700. Accessed 20.04.2021.
  16. Food and Agriculture Organization of the United Nations. Report of the 1995 Joint FAO/WHO meeting of experts for captan. Available at: https://www.fao.org/fileadmin/templates/agphome/documents/Pests_Pesticides/JMPR/Reports_1991-2006/Report1995.pdf. Accessed 20.04.2021.
  17. Bukowska B. Toxicity of 2,4-Dichlorophenoxyacetic Acid – Molecular Mechanisms. Polish Journal of Enviromental Studies. 2006; 15 (3): 365-74.
  18. Loomis D., Guyton K.Z., Grosse Y., El Ghissasi F., Bouvard V., Benbrachim- Talla L. et al. Carcinogenicity of lindane, DDT, and 2, 4-dichlorophenoxyacetic acid. The Lancet. Oncology. 2005; 16 (8): 891. https://doi.org/10.1016/S1470-2045(15)00081-9
  19. Food and Agriculture Organization of the United Nations. FAO specifications and evaluations for glyphosate. Available at: https://www.fao.org/fileadmin/templates/agphome/documents/Pests_Pesticides/Specs/Glypho_2014.pdf. Accessed 20.04.2021.
  20. Koller V.J., Fürhacker M., Nersesyan A., Mišík M., Eisenbauer M., Knasmueller S. Cytotoxic and DNA-damaging properties of glyphosate and Roundup in human-derived buccal epithelial cells. Archives of Toxicology. 2012; 86 (5): 805-13. https://doi.org/10.1007/s00204-012-0804-8
  21. Mañas F., Peralta L., Raviolo J., Ovando H.G., Weyers A., Ugnia L. et al. Genotoxicity of glyphosate assessed by the comet assay and cytogenetic tests. Environmental Toxicology and Pharmacology. 2009; 28 (1): 37-41. https://doi.org/10.1016/j.etap.2009.02.001
  22. Bolognesi C., Carrasquilla G., Volpi S., Solomon K.R., Marshall E.J. Biomonitoring of genotoxic risk in agricultural workers from five Colombian regions: association to occupational exposure to glyphosate. Journal of Toxicology and Environmental Health, Part A. 2009; 72 (15-16): 986-97. https://doi.org/10.1080/15287390902929741
  23. Guyton K.Z., Loomis D., Grosse Y., El Ghissassi F., Benbrahim-Tallaa L., Guha N. at al. International Agency for Research on Cancer Monograph Working Group ILF. Carcinogenicity of tetrachlorvinphos, parathion, malathion, diazinon, and glyphosate. The Lancet Oncology. 2015; 16 (5): 490-1. https://doi.org/10.1016/S1470-2045(15)70134-8
  24. Snyder R. D. Effects of Captan on DNA and DNA metabolic processes in human diploid fibroblasts. Environmental and Molecular Mutagenesis. 1992; 20 (2): 127-33. https://doi.org/10.1002/em.2850200208
  25. Lebailly P., Devaux A., Pottier D., De Meo M., Andre V., Baldi I. et al. Urine mutagenicity and lymphocyte DNA damage in fruit growers occupationally exposed to the fungicide captan. Occupational and environmental medicine. 2003; 60 (12): 910-7. https://doi.org/10.1136/oem.60.12.910
  26. European Food Safety Authority. Conclusion regarding the peer review of the pesticide risk assessment of the active substance fludioxonil. Available at: https://www.efsa.europa.eu/en/efsajournal/pub/rn-110. Accessed 20.04.2021.
  27. Environmental Protection Agency. Fludioxonil (Novartis). Pesticide Tolerances. Final Rule. Federal Register Online via GPO Access. 1998; 63 (194): 53820-6.
  28. European Food Safety Authority. Conclusion regarding the peer review of the pesticide risk assessment of the active substance fludioxonil. Available at: https://www.efsa.europa.eu/en/efsajournal/pub/rn-110. Accessed 20.04.2021.
  29. Graillot V., Takakura N., Hegarat L.L., Fessard V., Audebert M., Cravedi J.P. Genotoxicity of pesticide mixtures present in the diet of the French population. Environmental and Molecular Mutagenesis. 2012; 53(3): 173-84. https://doi.org/10.1002/em.21676.
  30. Bubalo N.N., Balan G.M. Lesion of the hepatobiliary system, oxidative stress and differentiated use of antioxidants in patients with acute and chronic intoxication with pesticides. Ukrainian Journal of Modern problems of toxicology [Ukrainskij zhurnal sovremennyh problem toksikologii]. 2017; 4 (80): 45-55. (in Russian)

Supplementary files

Supplementary Files
Action
1. JATS XML

Copyright (c) 2021 Averianova N.S., Kara L.A., Egorova O.V., Ilyushina N.A.



СМИ зарегистрировано Федеральной службой по надзору в сфере связи, информационных технологий и массовых коммуникаций (Роскомнадзор).
Регистрационный номер и дата принятия решения о регистрации СМИ: серия ПИ № ФС 77 - 81728 от 11 декабря 2013.