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Is micronucleus assay in oral exfoliated cells a useful biomarker for biomonitoring populations exposed to pesticides? A systematic review with meta-analysis

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Abstract

The systematic review (SR) with meta-analysis aimed to infer if micronucleus assay using oral mucosal cells a useful biomarker for biomonitoring populations continuously exposed to pesticides (EP). The SR has been made in accordance with the PRISMA-P guidelines. The PICOS strategy has focused to answer the following question: “Does exposure to pesticides cause genetic damage in oral cells?” The literature search was made in the following scientific databases: Web of Science, PubMed/Medline, and Scopus. The approach was defined as follows: standardized mean difference (SMD) and 95% confidence intervals (CI). The quality assessment of manuscripts was obtained by the EPHPP (Effective Public Health Practice Project). The GRADE tool was chosen for assessing the quality of evidence. A total of 108 articles were selected in this setting. After screening abstracts and titles, 23 manuscripts were evaluated for eligibility. After reviewing the studies, two were considered weak and 22 were classified as moderate or strong. The meta-analysis data pointed out statistically significant differences in volunteers exposed to EP (SMD = 1.23, 95% CI, 0.69 to 1.77, p < 0.001), with a Tau2 = 1.44; Chi2 = 566.38, and p < 0.001, so that the selected manuscripts were considered heterogeneous and the I2 of 97% indicated high heterogeneity. Taken together, this review was able to validate the micronucleus assay in oral exfoliated cells as a useful biomarker in individuals continuously exposed to EP because the studies categorized as moderate and strong have demonstrated positive response related to mutagenesis.

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References

  • Angelieri F, Joias RP, Bresciani E, Noguti J, Ribeiro DA (2012) Orthodontic cements induce genotoxicity and cytotoxicity in mammalian cells in vitro. Dent Res J (isfahan) 9(4):393–398

    CAS  Google Scholar 

  • Angerer J, Ewers U, Wilhelm M (2007) Human biomonitoring: state of the art. Int J Hyg Environ Health 210(3–4):201–228

    Article  CAS  Google Scholar 

  • Arévalo-Jaramillo P, Idrobo A, Salcedo L, Cabrera A, Vintimilla A, Carrión M, Bailon-Moscoso N (2019) Biochemical and genotoxic effects in women exposed to pesticides in Southern Ecuador. Environ Sci Pollut Res Int 26(24):24911–24921

    Article  CAS  Google Scholar 

  • Balshem H, Helfand M, Schünemann HJ, Oxman AD, Kunz R, Brozek J et al (2011) GRADE guidelines: 3. Rating the quality of evidence. J Clin Epidemiol 64:401–406

    Article  Google Scholar 

  • Barrón Cuenca J, de Oliveira Galvão MF, Ünlü Endirlik B, Tirado N, Dreij K (2022) In vitro cytotoxicity and genotoxicity of single and combined pesticides used by Bolivian farmers. Environ Mol Mutagen 63(1):4–17

    Article  CAS  Google Scholar 

  • Basso CG, de Araujo-Ramos AT, Martino-Andrade AJ (2022) Exposure to phthalates and female reproductive health: a literature review. Reprod Toxicol S0890–6238(22):00026

    Google Scholar 

  • Benedetti D, Nunes E, Sarmento M, Porto C, Dos Santos CE, Dias JF, da Silva J (2013) Genetic damage in soybean workers exposed to pesticides: evaluation with the comet and buccal micronucleus cytome assays. Mutat Res 752(1–2):28–33

    Article  CAS  Google Scholar 

  • Benedetti D, Lopes Alderete B, de Souza CT, Ferraz Dias J, Niekraszewicz L, Cappetta M, Martínez-López W, Da Silva J (2018) DNA damage and epigenetic alteration in soybean farmers exposed to complex mixture of pesticides. Mutagenesis 33(1):87–95

    Article  CAS  Google Scholar 

  • Boettcher M, Kosmehl T, Braunbeck T (2011) Low-dose effects and biphasic effect profiles: is trenbolone a genotoxicant? Mutat Res 723(2):152–157

    Article  CAS  Google Scholar 

  • Bolognesi C, Bonassi S, Knasmueller S, Fenech M, Bruzzone M, Lando C, Ceppi M (2015) Clinical application of micronucleus test in exfoliated buccal cells: a systematic review and metanalysis. Mutat Res 766:20–31

    Article  CAS  Google Scholar 

  • Carbajal-López Y, Gómez-Arroyo S, Villalobos-Pietrini R, Calderón-Segura ME, Martínez-Arroyo A (2016) Biomonitoring of agricultural workers exposed to pesticide mixtures in Guerrero state, Mexico, with comet assay and micronucleus test. Environ Sci Pollut Res Int 23(3):2513–2520

    Article  CAS  Google Scholar 

  • Claudio SR, Simas JMM, Souza ACF, DO Carmo Baracho DE, Alencar M, Yamauchi LY, Ribeiro DA (2019) Genomic instability and cytotoxicity in buccal mucosal cells of workers in banana farming evaluated by micronucleus test. Anticancer Res 39(3):1283-1286

  • Cobanoglu H, Coskun M, Coskun M, Çayir A (2019) Results of buccal micronucleus cytome assay in pesticide-exposed and non-exposed group. Environ Sci Pollut Res Int 26(19):19676–19683

    Article  CAS  Google Scholar 

  • Countryman PI, Heddle JA (1976) The production of micronuclei from chromosome aberrations in irradiated cultures of human lymphocytes. Mutat Res 41(2–3):321–332

    Article  CAS  Google Scholar 

  • Da Silva FR, Da Silva J, Nunes E, Benedetti D, Kahl V, Rohr P, Abreu MB, Thiesen FV, Kvitko K (2012) Application of the buccal micronucleus cytome assay and analysis of PON1Gln192Arg and CYP2A6*9(-48T>G) polymorphisms in tobacco farmers. Environ Mol Mutagen 53(7):525–534

    Article  CAS  Google Scholar 

  • De Bortoli GM, de Azevedo MB, da Silva LB (2009) Cytogenetic biomonitoring of Brazilian workers exposed to pesticides: micronucleus analysis in buccal epithelial cells of soybean growers. Mutat Res 675(1–2):1–4

    Google Scholar 

  • de Oliveira AFB, de Souza MR, Benedetti D, Scotti AS, Piazza LS, Garcia ALH, Dias JF, Niekraszewicz LAB, Duarte A, Bauer D, Amaral L, Bassi Branco CL, de Melo RÉ, da Silva FR, da Silva J (2019) Investigation of pesticide exposure by genotoxicological, biochemical, genetic polymorphic and in silico analysis. Ecotoxicol Environ Saf 179:135–142

    Article  CAS  Google Scholar 

  • de Souza DV, Dos Anjos RB, Takeshita WM, de Barros VM, Nagaoka MR, Dos Santos JN (2022) Ribeiro DA (2022) Is micronucleus assay in oral exfoliated cells a suitable biomarker for predicting cancer risk in individuals with oral potentially malignant disorders? A systematic review with meta-analysis. Pathol Res Pract 232:153828

    Article  CAS  Google Scholar 

  • Dhillon VS, Deo P, Bonassi S, Fenech M (2021) Lymphocyte micronuclei frequencies in skin, haematological, prostate, colorectal and esophageal cancer cases: a systematic review and meta-analysis. Mutat Res 787:108372

    Article  CAS  Google Scholar 

  • Dutta S, Bahadur M (2016) Cytogenetic analysis of micronuclei and cell death parameters in epithelial cells of pesticide exposed tea garden workers. Toxicol Mech Methods 26(8):627–634

    Article  CAS  Google Scholar 

  • Ergene S, Celik A, Cavaş T, Kaya F (2007) Genotoxic biomonitoring study of population residing in pesticide contaminated regions in Goksu Delta: micronucleus, chromosomal aberrations and sister chromatid exchanges. Environ Int 33(7):877–885

    Article  CAS  Google Scholar 

  • Fenech M (2000) The in vitro micronucleus technique. Mutat Res 455(1–2):81–95

    Article  CAS  Google Scholar 

  • Foucault A, Ravalet N, Besombes J, Picou F, Gallay N, Babin L, Bourgeais J, Hamard S, Domenech J, Loyer P, Vallet N, Lejeune J, Gyan E, Béné MC, Vallette F, Olivier C, Hérault O (2021) Low-dose pesticides alter primary human bone marrow mesenchymal stem/stromal cells through ALDH2 inhibition. Cancers (basel) 13(22):5699

    Article  CAS  Google Scholar 

  • Gatto NM, Ogata P, Lytle B (2021) Farming, pesticides, and brain cancer: a 20-year updated systematic literature review and meta-analysis. Cancers (basel) 13(17):4477

    Article  Google Scholar 

  • Holland N, Bolognesi C, Kirsch-Volders M, Bonassi S, Zeiger E, Knasmueller S, Fenech M (2008) The micronucleus assay in human buccal cells as a tool for biomonitoring DNA damage: the HUMN project perspective on current status and knowledge gaps. Mutat Res 659(1–2):93–108

    Article  CAS  Google Scholar 

  • Hutter HP, Khan AW, Lemmerer K, Wallner P, Kundi M, Moshammer H (2018) cytotoxic and genotoxic effects of pesticide exposure in male coffee farmworkers of the Jarabacoa Region, Dominican Republic. Int J Environ Res Public Health 15(8):1641

    Article  CAS  Google Scholar 

  • Kausar A, Giri S, Roy P, Giri A (2014) Changes in buccal micronucleus cytome parameters associated with smokeless tobacco and pesticide exposure among female tea garden workers of Assam, India. Int J Hyg Environ Health 217(2–3):169–175

    Article  CAS  Google Scholar 

  • Kim SA, Lee H, Park SM, Kim MJ, Lee YM, Yoon YR, Lee HK, Moon HB, Lee IK, Lee DH (2022) Effect of low-dose persistent organic pollutants on mitochondrial function: human and in vitro evidence. Diabetes Metab J. in press.

  • Lemos AT, de Lemos CT, Coronas MV, da Rocha JR, Vargas VMF (2020) Integrated study of genotoxicity biomarkers in schoolchildren and inhalable particles in areas under petrochemical influence. Environ Res 188:109443

    Article  CAS  Google Scholar 

  • Li Z (2022) Quantifying exposure source allocation factors of pesticides in support of regulatory human health risk assessment. J Environ Manage 309:114697

    Article  CAS  Google Scholar 

  • Lucero L, Pastor S, Suárez S, Durbán R, Gómez C, Parrón T, Creus A, Marcos R (2000) Cytogenetic biomonitoring of Spanish greenhouse workers exposed to pesticides: micronuclei analysis in peripheral blood lymphocytes and buccal epithelial cells. Mutat Res 464(2):255–262

    Article  CAS  Google Scholar 

  • Luna-Carrascal J, Quintana-Sosa M, Olivero-Verbel J (2022) Genotoxicity biomarkers in car repair workers from Barranquilla, a Colombian Caribbean City. J Toxicol Environ Health A 85(7):263–275

    Article  CAS  Google Scholar 

  • Malacarne IT, De Souza DV, Alpire MES, Souza ACF, Renno ACM, Ribeiro DA (2021) EIs micronucleus assay in oral exfoliated cells a suitable tool for biomonitoring children exposed to environmental pollutants A systematic review. Environ Sci Pollut Res Int 28(46):65083–65093

    Article  CAS  Google Scholar 

  • Martínez-Valenzuela C, Waliszewski SM, Amador-Muñoz O, Meza E, Calderón-Segura ME, Zenteno E, Huichapan-Martínez J, Caba M, Félix-Gastélum R, Longoria-Espinoza R (2017) Aerial pesticide application causes DNA damage in pilots from Sinaloa, Mexico. Environ Sci Pollut Res Int 24(3):2412–2420

    Article  CAS  Google Scholar 

  • Melaram R (2021) Environmental risk factors implicated in liver disease: a mini-review. Front Public Health 9:683719

    Article  Google Scholar 

  • Milić M, Gerić M, Nodilo M, Ranogajec-Komor M, Milković Đ, Gajski G (2020) Application of the buccal micronucleus cytome assay on child population exposed to sinus X-ray. Eur J Radiol 129:109143

    Article  Google Scholar 

  • Nersesyan A, Kundi M, Atefie K, Schulte-Hermann R, Knasmüller S (2006) Effect of staining procedures on the results of micronucleus assays with exfoliated oral mucosa cells. Cancer Epidemiol Biomarkers Prev 15(10):1835–1840

    Article  CAS  Google Scholar 

  • Panico A, Grassi T, Bagordo F, Idolo A, Serio F, Tumolo MR, De Donno A (2020) Micronucleus frequency in exfoliated buccal cells of children living in an industrialized area of Apulia (Italy). Int J Environ Res Public Health 17(4):1208

    Article  Google Scholar 

  • Pastor S, Creus A, Xamena N, Siffel C, Marcos R (2002) Occupational exposure to pesticides and cytogenetic damage: results of a Hungarian population study using the micronucleus assay in lymphocytes and buccal cells. Environ Mol Mutagen 40(2):101–109

    Article  CAS  Google Scholar 

  • Pastor S, Gutiérrez S, Creus A, Cebulska-Wasilewska A, Marcos R (2001a) Micronuclei in peripheral blood lymphocytes and buccal epithelial cells of Polish farmers exposed to pesticides. Mutat Res 495(1–2):147–156

    Article  CAS  Google Scholar 

  • Pastor S, Gutiérrez S, Creus A, Xamena N, Piperakis S, Marcos R (2001b) Cytogenetic analysis of Greek farmers using the micronucleus assay in peripheral lymphocytes and buccal cells. Mutagenesis 16(6):539–545

    Article  CAS  Google Scholar 

  • Remor AP, Totti CC, Moreira DA, Dutra GP, Heuser VD, Boeira JM (2009) Occupational exposure of farm workers to pesticides: biochemical parameters and evaluation of genotoxicity. Environ Int 35(2):273–278

    Article  CAS  Google Scholar 

  • Sailaja N, Chandrasekhar M, Rekhadevi PV, Mahboob M, Rahman MF, Vuyyuri SB, Danadevi K, Hussain SA, Grover P (2006) Genotoxic evaluation of workers employed in pesticide production. Mutat Res 609(1):74–80

    Article  CAS  Google Scholar 

  • Sonzogni L, Ferlazzo ML, Granzotto A, Fervers B, Charlet L, Foray N (2022) DNA double-strand breaks induced in human cells by 6 current pesticides: intercomparisons and influence of the ATM protein. Biomolecules 12(2):250

    Article  CAS  Google Scholar 

  • Sram RJ, Svecova V, Rossnerova A (2016) Systematic review of the use of the lymphocyte cytokinesis-block micronucleus assay to measure DNA damage induced by exposure to polycyclic aromatic hydrocarbons. Mutat Res Rev Mutat Res 770:162–169

    Article  CAS  Google Scholar 

  • Thomas BH, Ciliska D, Dobbins M, Micucci S (2004) A process for systematically reviewing the literature: providing the research evidence for public health nursing interventions. Worldviews Evid Based Nurs 1:176–184

    Article  CAS  Google Scholar 

  • Tolbert PE, Shy CM, Allen JW (1992) Micronuclei and other nuclear anomalies in buccal smears: methods development. Mutat Res 271(1):69–77

    Article  CAS  Google Scholar 

  • Tomiazzi JS, Judai MA, Nai GA, Pereira DR, Antunes PA, Favareto APA (2018) Evaluation of genotoxic effects in Brazilian agricultural workers exposed to pesticides and cigarette smoke using machine-learning algorithms. Environ Sci Pollut Res Int 25(2):1259–1269

    Article  CAS  Google Scholar 

  • Valencia-Quintana R, López-Durán RM, Milić M, Bonassi S, Ochoa-Ocaña MA, Uriostegui-Acosta MO, Pérez-Flores GA, Gómez-Olivares JL, Sánchez-Alarcón JA (2021) Assessment of cytogenetic damage and cholinesterases’ activity in workers occupationally exposed to pesticides in Zamora-Jacona, Michoacan, Mexico. Int J Environ Res Public Health 18(12):6269

    Article  CAS  Google Scholar 

  • Varghese JV, Sebastian EM, Iqbal T, Tom AA (2020) Pesticide applicators and cancer: a systematic review. Rev Environ Health 36(4):467–476

    Article  CAS  Google Scholar 

  • Vervaet BA, Nast CC, Schreurs G, Jayasumana C, Herath C, Kojc N, De Broe ME (2021) Chronic interstitial nephritis in agricultural communities: a new perspective on etiology, diagnosis and mechanism. Nephrol Ther 17S:S45–S50

    Article  Google Scholar 

  • Wilhelm CM, Calsing AK, da Silva LB (2015) Assessment of DNA damage in floriculturists in southern Brazil. Environ Sci Pollut Res Int 22(11):8182–8189

    Article  CAS  Google Scholar 

  • Yu G, Su Q, Chen Y, Wu L, Wu S, Li H (2021) Epigenetics in neurodegenerative disorders induced by pesticides. Genes Environ 43(1):55

    Article  CAS  Google Scholar 

  • Zhao W, Teng M, Zhang J, Wang K, Zhang J, Xu Y, Wang C (2022) Insights into the mechanisms of organic pollutant toxicity to earthworms: advances and perspectives. Environ Pollut 10:119120

    Article  CAS  Google Scholar 

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Funding

The authors acknowledge research grants received from CNPq (Conselho Nacional de Desenvolvimento Cientifico e Tecnológico) and CAPES. DVS thanks CAPES (Coordenação de Aperfeiçoamento de Pessoal de Nível Superior) for grants received scholarship. MBV, ACMR, and DAR thank CNPq for productivity fellowships.

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Study design: DVS, BAR, and DAR. Data search: DVS, BAR, and DAR. Data analysis: DVS, BAR, WMT, MBV, ACMR, and DAR. Writing the paper: all authors.

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Correspondence to Daniel Araki Ribeiro.

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Malacarne, I.T., Takeshita, W.M., de Souza, D.V. et al. Is micronucleus assay in oral exfoliated cells a useful biomarker for biomonitoring populations exposed to pesticides? A systematic review with meta-analysis. Environ Sci Pollut Res 29, 64392–64403 (2022). https://doi.org/10.1007/s11356-022-22015-x

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