Email this article Effect of a phthalimide pesticide on human peripheral blood lymphocytes in vitro: induction of DNA damage
- Authors: Tsareva A.A.1, Ignatyev S.D.1, Egorova O.V.1, Kotnova A.P.1, Averianova N.S.1, Ilyushina N.A.1
-
Affiliations:
- FBES “Federal Scientific Center of Hygiene named after F.F. Erisman” of the Federal Service for Surveillance on Consumer Rights Protection and Human Wellbeing
- Issue: No 6 (2023)
- Pages: 376-384
- Section: Original articles
- Published: 15.01.2024
- URL: https://rjsocmed.com/0869-7922/article/view/641508
- DOI: https://doi.org/10.47470/0869-7922-2023-31-6-376-384
- EDN: https://elibrary.ru/orykxh
- ID: 641508
Cite item
Open Access
Access granted
Subscription Access
Abstract
Introduction. Captan is a contact fungicide from the phthalimide class, used in agriculture to combat plant diseases. However, the question of its genotoxicity for humans remains open. Various studies examining the mutagenic activity of captan using different tests have yielded conflicting results. This study aims to investigate the potential of captan to induce DNA damage in human peripheral blood lymphocytes in vitro using single-cell alkaline gel electrophoresis.
Material and methods. The DNA-damaging effect of captan (0; 2.5; 5.0; 10.0; 12.5 and 25 µg/ml) on lymphocytes of 26 donors was assessed with metabolic activation (+S9) and without it (–S9) using DNA comet analysis.
Results. In the absence of metabolic activation, captan exhibited a pronounced genotoxic effect on cells. Statistically significant effects of captan was found on lymphocytes of all donors. The level of DNA-damaging effect on lymphocytes from 20 out of 26 donors depended on the concentration. The fold increase in the “%DNA in the tail of comets” indicator compared to the negative control at a concentration of 25 µg/ml varied in the range of 4,3–226 times. In the presence of the S9 mixture, weak but significant effects meeting the criteria for a positive response were detected only in three donors.
Limitations. The genotoxicity of captan was studied only in vitro.
Conclusion. Captan induces DNA damage in human peripheral blood lymphocytes in vitro in the absence of metabolic activation. Under conditions of metabolic activation, genotoxic effects were low. The levels of DNA damage in peripheral blood lymphocytes of different donors after exposure to captan varied markedly, indicating the necessity to consider individual sensitivity to genotoxicants when utilizing the DNA comet method to assess the potential mutagenic activity of chemicals.
Compliance with ethical standards. The study was approved by the Ethics Committee of the Federal Scientific Center for Hygiene. F.F. Erisman” of Rospotrebnadzor (Protocol No. 1, September 29, 2020).
Author contribution:
Tsareva A.A. — the collection of material;
Ignatyev S.D. — processing of material;
Egorova O.V. — concept and design of the study, collecting and processing of material, analysis of the results; writing the text;
Kotnova A.P. — the collection of material;
Averianova N.S. — the collection of material;
Ilyushina N.A. — concept and design of the study, processing of material, analysis of the results; writing the text.
All authors are responsible for the integrity of all parts of the manuscript and approval of the manuscript final version.
Conflict of interests. The authors declare no conflict of interest.
Funding. The study had no sponsorship.
Date of receipt: November 10, 2023 / Date of acceptance for printing: December 3, 2023 / Date of publication: December 29, 2023
About the authors
Anastasiya A. Tsareva
FBES “Federal Scientific Center of Hygiene named after F.F. Erisman” of the Federal Service for Surveillance on Consumer Rights Protection and Human Wellbeing
Author for correspondence.
Email: grabovskaya.aa@fncg.ru
ORCID iD: 0000-0002-3479-9602
Junior researcher of the department of genetic toxicology, FBES “Federal Scientific Center of Hygiene named after F.F. Erisman” of the Federal Service for Surveillance on Consumer Rights Protection and Human Wellbeing, 141014, Moscow region, Mytishchi, Russian Federation
e-mail: grabovskaya.aa@fncg.ru
Russian FederationSemen D. Ignatyev
FBES “Federal Scientific Center of Hygiene named after F.F. Erisman” of the Federal Service for Surveillance on Consumer Rights Protection and Human Wellbeing
Email: ignatev.sd@fncg.ru
ORCID iD: 0000-0001-7415-5513
Junior researcher of the department of genetic toxicology, FBES “Federal Scientific Center of Hygiene named after F.F. Erisman” of the Federal Service for Surveillance on Consumer Rights Protection and Human Wellbeing, 141014, Moscow region, Mytishchi, Russian Federation
e-mail: ignatev.sd@fncg.ru
Russian FederationOlga V. Egorova
FBES “Federal Scientific Center of Hygiene named after F.F. Erisman” of the Federal Service for Surveillance on Consumer Rights Protection and Human Wellbeing
Email: egorova.ov@fncg.ru
ORCID iD: 0000-0003-4748-8771
Candidate of Biological Sciences, senior Researcher of the department of genetic toxicology, FBES “Federal Scientific Center of Hygiene named after F.F. Erisman” of the Federal Service for Surveillance on Consumer Rights Protection and Human Wellbeing, 141014, Moscow region, Mytishchi, Russian Federation
e-mail: egorova.ov@fncg.ru
Russian FederationAlina P. Kotnova
FBES “Federal Scientific Center of Hygiene named after F.F. Erisman” of the Federal Service for Surveillance on Consumer Rights Protection and Human Wellbeing
Email: kotnova.ap@fncg.ru
ORCID iD: 0000-0002-4333-9288
Candidate of Biological Sciences, senior researcher of the department of genetic toxicology, FBES “Federal Scientific Center of Hygiene named after F.F. Erisman” of the Federal Service for Surveillance on Consumer Rights Protection and Human Wellbeing, 141014, Moscow region, Mytishchi, Russian Federation
e-mail: kotnova.ap@fncg.ru
Russian FederationNatalya S. Averianova
FBES “Federal Scientific Center of Hygiene named after F.F. Erisman” of the Federal Service for Surveillance on Consumer Rights Protection and Human Wellbeing
Email: averyanova.ns@fncg.ru
ORCID iD: 0000-0002-2973-8776
Candidate of Biological Sciences, senior researcher of the department of genetic toxicology, FBES “Federal Scientific Center of Hygiene named after F.F. Erisman” of the Federal Service for Surveillance on Consumer Rights Protection and Human Wellbeing, 141014, Moscow region, Mytishchi, Russian Federation
e-mail: averyanova.ns@fncg.ru
Russian FederationNataliya A. Ilyushina
FBES “Federal Scientific Center of Hygiene named after F.F. Erisman” of the Federal Service for Surveillance on Consumer Rights Protection and Human Wellbeing
Email: ilushina.na@fncg.ru
ORCID iD: 0000-0001-9122-9465
D.Sc. (Biology), Head of the department of genetic toxicology, FBES “Federal Scientific Center of Hygiene named after F.F. Erisman” of the Federal Service for Surveillance on Consumer Rights Protection and Human Wellbeing
e-mail: ilushina.na@fncg.ru
Russian FederationReferences
- Elliot Gordon Independent Researcher. Captan and Folpet December 2010. In: Hayes’ Handbook of Pesticide Toxicology. 1915–9. https://doi.org/10.1016/B978-0-12-374367-1.00090-2
- Fedorova N.E., Bereznyak I.V., Bondareva L.G., Dobreva N.I., Egorchenkova O.E., Dobrev S.D. Captan: Problems Associated with its Identification in Environmental Objects and Food Products. Ways of Solution. Chemical safety of food products. 2022; 6(2): 227–42. Yttps//doi.org/10.25514/CHS.2022.2.23015 (In Russian)
- Mary Ann Liebert, Inc., Publishers. Final Report on the Safety Assessment of Captan. Journal of the American college of toxicology. 1989; 8(4): 643–80. https://journals.sagepub.com/doi/pdf/10.3109/10915818909010526
- 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.
- Averianova N.S., Kara L.A., Egorova O.V., Ilyushina N.A. The study of primary DNA damage under the combined action of pesticides. Toksikologicheskiy vestnik (Toxicological Review). 2021; 29(4): 14–21. https://doi.org/10.36946/0869-7922-2021-29-4-14-21 (In Russian)
- Egorova O.V., Ilyushina N.A., Rakitskii V.N. Mutagenicity evaluation of pesticide analogs using standard and 6-well miniaturized bacterial reverse mutation tests. Toxicology in Vitro. 2020; 69: 105006. https://doi.org/10.1016/j.tiv.2020.105006
- Greenburg D.L., Rusiecki J., Koutros S., Dosemeci M., Patel R., Hines C.J., Hoppin J.A., Alavanja M.C. Cancer incidence among pesticide applicators exposed to captan in the Agricultural Health Study. Cancer Causes Control. 2008; 19(10): 1401–7. https://doi.org/10.1007/s10552-008-9187-9
- Lebailly P., Devaux A., Pottier D., De Meo M., Andre V., Baldi I., Severin F., Bernaud J., Durand B., Henry-Amar M., Gauduchon P. Urine mutagenicity and lymphocyte DNA damage in fruit growers occupationally exposed to the fungicide captan. Occup Environ Med. 2003; 60(12): 910–7. https://doi.org/10.1136/oem.60.12.910
- Presutti R., Harris S.A., Kachuri L., Spinelli J.J., Pahwa M., Blair A., Zahm S.H., Cantor K.P., Weisenburger D.D., Pahwa P., McLaughlin J.R., Dosman J.A., Freeman L.B. Pesticide exposures and the risk of multiple myeloma in men: An analysis of the North American Pooled Project. Int J Cancer. 2016; 139(8): 1703–14. https://doi.org/10.1002/ijc.30218
- De Hondt H.A., Ali S.M., El-laithy A.F. Biochemical and chromosomal studies on rats injected with captan. Egypt. J. Genet. Cytol. 1982; 11(2): 245–54.
- Ilyushina N.A. Systematic assessment of the genotoxicity of pesticides in the Russian Federation: Diss. Moscow; 2020. (in Russian)
- Gordon E.B., Mobley S.C., Ehrlich T., Williams M. Measurement of the reaction between the fungicides captan or folpet and blood thiols. Toxicol. Methods. 2001; 11: 209–23.
- Fernandez-Vidal A., Arnaud L.C., Maumus M., Chevalier M., Mirey G., Salles B., Vignard J., Boutet-Robinet E. Exposure to the Fungicide Captan Induces DNA Base Alterations and Replicative Stress in Mammalian Cells. Environ Mol Mutagen. 2019; 60(3): 286–97. https://doi.org/10.1002/em.22268
Supplementary files
