Abstract
Micronuclei (MN) are originated when a whole or broken chromosome/chromatin lag at the anaphase of dividing cells and becomes separated from the main chromatin during telophase. The test to detect this structure in lymphocytes, the cytokinesis-block micronucleus cytome (CBMN-Cyt) assay, has been used for over 40 years and it is still being applied in new and promising areas of biology, health, and nanotechnology. It can be used to assess the genotoxic effect derived from occupational and environmental exposure or because of having a chronic disease. In addition, the test can be considered an indirect measure of prognosis in clinical studies. The present chapter reviews different studies that describe the formation of MN in lymphocytes and the associations of the increase of MN in individuals exposed environmentally and occupationally to different genotoxic agents. In addition, this chapter brings some results of this biomarker of genomic instability and its relation with different diseases.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Similar content being viewed by others
Abbreviations
- AD:
-
Alzheimer’s disease
- ALS:
-
Amyotrophic lateral sclerosis
- AT:
-
Ataxia telangiectasia
- AUD:
-
Autoimmune diseases
- BFB:
-
Breakage-fusion-bridge
- BN:
-
Binucleate cells
- CAD:
-
Coronary artery disease
- CBMN-Cyt:
-
Cytokinesis-block micronucleus cytome
- CKD:
-
Chronic kidney disease
- COPD:
-
Chronic obstructive pulmonary disease
- CRC:
-
Colorectal cancer
- CS:
-
Cockayne’s syndrome
- DNA:
-
Deoxyribonucleic acid
- DS:
-
Down syndrome
- FAL:
-
Formaldehyde
- GTS:
-
Green tobacco sickness
- HNC:
-
Head and neck cancers
- IARC:
-
International Agency for Research on Cancer
- MCI:
-
Mild cognitive impairment
- MN:
-
Micronuclei
- NBUD:
-
Nuclear buds
- NPB:
-
Nucleoplasmic bridges
- NSCL/P:
-
Non-syndromic orofacial clefts and/or palate
- NTD:
-
Neural tube defects
- PAH:
-
Polycyclic aromatic hydrocarbons
- PD:
-
Parkinson’s diseases
- ROS:
-
Reactive oxygen species
- SIL:
-
Squamous intraepithelial lesions
- T2D:
-
Type 2 diabetes
- WS:
-
Werner’s syndrome
- XP:
-
Xeroderma pigmentosum
References
Andreassi MG, Borghini A, Vecoli C (2021) Micronucleus assay for predicting coronary artery disease: A systematic review and meta-analysis. Mutat Res Mutat Res 787:108348. https://doi.org/10.1016/J.MRREV.2020.108348
Angerer J, Ewers U, Wilhelm M. Human biomonitoring: state of the art. Int J Hyg Environ Health. 2007;210:201–28. https://doi.org/10.1016/j.ijheh.2007.01.024.
Annangi B, Bonassi S, Marcos R, Hernández A. Biomonitoring of humans exposed to arsenic, chromium, nickel, vanadium, and complex mixtures of metals by using the micronucleus test in lymphocytes. Mutat Res. 2016;770:140–61. https://doi.org/10.1016/J.MRREV.2016.03.003.
Antonini JM. Health effects of welding. Crit Rev Toxicol. 2003;33:61–103. https://doi.org/10.1080/713611032.
Arcury TA, Quandt SA, Preisser JS, et al. High levels of transdermal nicotine exposure produce green tobacco sickness in Latino farmworkers. Nicotine Tob Res. 2003;5:315–21. https://doi.org/10.1080/1462220031000094132.
Asanov M, Bonassi S, Proietti S, et al. Genomic instability in chronic obstructive pulmonary disease and lung cancer: a systematic review and meta-analysis of studies using the micronucleus assay. Mutat Res. 2021;787:108344. https://doi.org/10.1016/J.MRREV.2020.108344.
Binici DN, Karaman A, Kadi M. Micronucleus analysis in Behcet’s disease with and without HLA-B51. Turkiye Fiz Tip ve Rehabil Derg. 2013;59:36–41. https://doi.org/10.4274/tftr.46873.
Bolognesi C, Holland N. The use of the lymphocyte cytokinesis-block micronucleus assay for monitoring pesticide-exposed populations. Mutat Res – Rev Mutat Res. 2016;770:183–203. https://doi.org/10.1016/j.mrrev.2016.04.006.
Bolognesi C, Martini F, Tognon M, et al. A molecular epidemiology case control study on pleural malignant mesothelioma. Cancer Epidemiol Biomark Prev. 2005;14:1741–6. https://doi.org/10.1158/1055-9965.EPI-04-0903.
Bolognesi C, Bruzzone M, Ceppi M, Marcon F. Micronuclei and upper body cancers (head, neck, breast cancers) a systematic review and meta-analysis. Mutat Res. 2021;787:108358. https://doi.org/10.1016/J.MRREV.2020.108358.
Bonassi S, Fenech M. Chapter 4 Micronuclei and their association with infertility, pregnancy complications, developmental defects, anaemias, inflammation, diabetes, chronic kidney disease, obesity, cardiovascular disease, neurodegenerative diseases and cancer. In: The micronucleus assay in toxicology. The Royal Society of Chemistry; 2019. p. 38–78. https://doi.org/10.1039/9781788013604-00038.
Bonassi S, Ugolini D, Kirsch-Volders M, et al. Human population studies with cytogenetic biomarkers: review of the literature and future prospectives. Environ Mol Mutagen. 2005;45:258–70. https://doi.org/10.1002/em.20115.
Botto N, Rizza A, Colombo MG, et al. Evidence for DNA damage in patients with coronary artery disease. Mutat Res Toxicol Environ Mutagen. 2001;493:23–30. https://doi.org/10.1016/S1383-5718(01)00162-0.
Burgaz S, Coskun E, Cakmak Demircigil G, et al. Micronucleus frequencies in lymphocytes and buccal epithelial cells from patients having head and neck cancer and their first-degree relatives. Mutagenesis. 2011;26:351–6. https://doi.org/10.1093/mutage/geq101.
Cakmak Demircigil G, Aykanat B, Fidan K, et al. Micronucleus frequencies in peripheral blood lymphocytes of children with chronic kidney disease. Mutagenesis. 2011;26:643–50. https://doi.org/10.1093/mutage/ger027.
Cardinale F, Bruzzi P, Bolognesi C. Role of micronucleus test in predicting breast cancer susceptibility: a systematic review and meta-analysis. Br J Cancer. 2012;106:780–90. https://doi.org/10.1038/bjc.2011.567.
Cheng TJ, Christiani DC, Xu X, et al. Increased micronucleus frequency in lymphocytes from smokers with lung cancer. Mutat Res Mol Mech Mutagen. 1996;349:43–50. https://doi.org/10.1016/0027-5107(95)00150-6.
Council NR. Human biomonitoring for environmental chemicals. Washington, DC: The National Academies Press; 2006. https://doi.org/10.17226/11700.
Da Silva J. DNA damage induced by occupational and environmental exposure to miscellaneous chemicals. Mutat Res. 2016;770:170–82. https://doi.org/10.1016/J.MRREV.2016.02.002.
Da Silva FR, Kvitko K, Rohr P, et al. Genotoxic assessment in tobacco farmers at different crop times. Sci Total Environ. 2014;490:334–41. https://doi.org/10.1016/j.scitotenv.2014.05.018.
De Souza MR, Dihl RR, Da Silva J. Chapter 34 Use of micronucleus assays to measure DNA damage caused by coal dust and ash. In: The micronucleus assay in toxicology. The Royal Society of Chemistry; 2019. p. 561–82. https://doi.org/10.1039/9781788013604-00561.
Dhillon VS, Deo P, Bonassi S, Fenech M. Lymphocyte micronuclei frequencies in skin, haematological, prostate, colorectal and esophageal cancer cases: a systematic review and meta-analysis. Mutat Res. 2021;787:108372. https://doi.org/10.1016/J.MRREV.2021.108372.
Donmez-Altuntas H, Sut Z, Ferahbas A, et al. Increased micronucleus frequency in phytohaemagglutinin-stimulated blood cells of patients with vitiligo. J Eur Acad Dermatol Venereol. 2008;22:162–7. https://doi.org/10.1111/j.1468-3083.2007.02356.x.
Donmez-Altuntas H, Sahin F, Bayram F, et al. Evaluation of chromosomal damage, cytostasis, cytotoxicity, oxidative DNA damage and their association with body-mass index in obese subjects. Mutat Res Toxicol Environ Mutagen. 2014;771:30–6. https://doi.org/10.1016/J.MRGENTOX.2014.06.006.
Droppelmann CA, Campos-Melo D, Moszczynski AJ, et al. TDP-43 aggregation inside micronuclei reveals a potential mechanism for protein inclusion formation in ALS. Sci Rep. 2019;9:19928. https://doi.org/10.1038/s41598-019-56483-y.
El-Zein RA, Schabath MB, Etzel CJ, et al. Cytokinesis-blocked micronucleus assay as a novel biomarker for lung cancer risk. Cancer Res. 2006;66:6449–56. https://doi.org/10.1158/0008-5472.CAN-06-0326.
Espitia-Pérez L, Arteaga-Pertuz M, Soto JS, et al. Geospatial analysis of residential proximity to open-pit coal mining areas in relation to micronuclei frequency, particulate matter concentration, and elemental enrichment factors. Chemosphere. 2018;206:203–16. https://doi.org/10.1016/J.CHEMOSPHERE.2018.04.049.
Fenech M. Cytokinesis-block micronucleus cytome assay. Nat Protoc. 2007;2:1084–104. https://doi.org/10.1038/nprot.2007.77.
Fenech M, Bonassi S. The effect of age, gender, diet and lifestyle on DNA damage measured using micronucleus frequency in human peripheral blood lymphocytes. Mutagenesis. 2011;26:43–9. https://doi.org/10.1093/mutage/geq050.
Fenech M, Nersesyan A, Knasmueller S. A systematic review of the association between occupational exposure to formaldehyde and effects on chromosomal DNA damage measured using the cytokinesis-block micronucleus assay in lymphocytes. Mutat Res. 2016;770:46–57. https://doi.org/10.1016/J.MRREV.2016.04.005.
Fenech M, Knasmueller S, Bolognesi C, et al. Micronuclei as biomarkers of DNA damage, aneuploidy, inducers of chromosomal hypermutation and as sources of pro-inflammatory DNA in humans. Mutat Res. 2020;786:108342. https://doi.org/10.1016/J.MRREV.2020.108342.
Franzke B, Schwingshackl L, Wagner KH. Chromosomal damage measured by the cytokinesis block micronucleus cytome assay in diabetes and obesity – a systematic review and meta-analysis. Mutat Res. 2020;786:108343. https://doi.org/10.1016/J.MRREV.2020.108343.
Furness DLF, Dekker GA, Hague WM, et al. Increased lymphocyte micronucleus frequency in early pregnancy is associated prospectively with pre-eclampsia and/or intrauterine growth restriction. Mutagenesis. 2010;25:489–98. https://doi.org/10.1093/mutage/geq032.
Gashi G, Mahovlić V, Manxhuka-Kerliu S, et al. The association between micronucleus, nucleoplasmic bridges, and nuclear buds frequency and the degree of uterine cervical lesions. Biomarkers. 2018;23:364–72. https://doi.org/10.1080/1354750X.2018.1428828.
George A, Dey R, Bhuria V, et al. Nuclear anomalies, chromosomal aberrations and proliferation rates in cultured lymphocytes of head and neck cancer patients. Asian Pac J Cancer Prev. 2014;15:1119–23. https://doi.org/10.7314/APJCP.2014.15.3.1119.
Gisselsson D, Jonson T, Yu C, et al. Centrosomal abnormalities, multipolar mitosis, and chromosomal instability in head and neck tumours with dysfunctional telomeres. Br J Cancer. 2002;87:202–7. https://doi.org/10.1038/sj.bjc.6600438.
Hamurcu Z, Dönmez-Altuntas H, Borlu M, et al. Micronucleus frequency in the oral mucosa and lymphocytes of patients with Behçet’s disease. Clin Exp Dermatol. 2005;30:565–9. https://doi.org/10.1111/j.1365-2230.2005.01876.x.
Hanahan D, Weinberg RA. The hallmarks of cancer review Douglas. Cell. 2000;100:57–70. https://doi.org/10.1016/s0092-8674(00)81683-9.
Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell. 2011;144:646–74. https://doi.org/10.1016/j.cell.2011.02.013.
Hayashi M. The micronucleus test-most widely used in vivo genotoxicity test. Genes Environ. 2016;38:18. https://doi.org/10.1186/s41021-016-0044-x.
IARC. Formaldehyde 2-butoxyethanol and 1-tert-butoxypropan-2-ol. International Agency for Research on Cancer, Lyon. IARC Monogr Eval Carcinog Risks Hum. 2006;88:1–478.
Kahl VFS, Dhillon VS, Simon D, et al. Chronic occupational exposure endured by tobacco farmers from Brazil and association with DNA damage. Mutagenesis. 2018;33:119–28. https://doi.org/10.1093/mutage/gex045.
Kapka-Skrzypczak L, Czajka M, Sawicki K, et al. Assessment of DNA damage in polish children environmentally exposed to pesticides. Mutat Res Toxicol Environ Mutagen. 2019;843:52–6. https://doi.org/10.1016/J.MRGENTOX.2018.12.012.
Karaman A, Binici DN, Kabalar ME, Calikuşu Z. Micronucleus analysis in patients with colorectal adenocarcinoma and colorectal polyps. World J Gastroenterol. 2008;14:6835–9. https://doi.org/10.3748/wjg.14.6835.
Karaman A, Kadı M, Kara F. Sister chromatid exchange and micronucleus studies in patients with Behçet’s disease. J Cutan Pathol. 2009;36:831–7. https://doi.org/10.1111/j.1600-0560.2008.01180.x.
Kirsch-Volders M, Bolognesi C, Ceppi M, et al. Micronuclei, inflammation and auto-immune disease. Mutat Res. 2020;786:108335. https://doi.org/10.1016/J.MRREV.2020.108335.
Knudsen LE, Kirsch-Volders M. Micronuclei, reproduction and child health. Mutat Res. 2021;787:108345. https://doi.org/10.1016/J.MRREV.2020.108345.
Lee SL, Thomas P, Hecker J, et al. Chromosomal DNA damage measured using the cytokinesis-block micronucleus cytome assay is significantly associated with cognitive impairment in South Australians. Environ Mol Mutagen. 2015;56:32–40. https://doi.org/10.1002/em.21890.
Lemos AT, de Lemos CT, Coronas MV, et al. Integrated study of genotoxicity biomarkers in school children and inhalable particles in areas under petrochemical influence. Environ Res. 2020;188:109443. https://doi.org/10.1016/J.ENVRES.2020.109443.
León-Mejía G, Espitia-Pérez L, Hoyos-Giraldo LS, et al. Assessment of DNA damage in coal open-cast mining workers using the cytokinesis-blocked micronucleus test and the comet assay. Sci Total Environ. 2011;409:686–91. https://doi.org/10.1016/j.scitotenv.2010.10.049.
Li X, Bai Y, Wang S, et al. Association of body mass index with chromosome damage levels and lung cancer risk among males. Sci Rep. 2015;5:9458. https://doi.org/10.1038/srep09458.
Lombardi S, Fuoco I, Di Fluri G, et al. Genomic instability and cellular stress in organ biopsies and peripheral blood lymphocytes from patients with colorectal cancer and predisposing pathologies. Oncotarget. 2015;6:14852–64. https://doi.org/10.18632/oncotarget.4032.
Longnecker MP, Klebanoff MA, Zhou H, Brock JW. Association between maternal serum concentration of the DDT metabolite DDE and preterm and small-for-gestational-age babies at birth. Lancet. 2001;358:110–4. https://doi.org/10.1016/S0140-6736(01)05329-6.
López-Otín C, Blasco MA, Partridge L, et al. The hallmarks of aging. Cell. 2013;153:1194–217. https://doi.org/10.1016/j.cell.2013.05.039.
Maffei F, Manuel J, Moraga Z, et al. Micronucleus frequency in human peripheral blood lymphocytes as a biomarker for the early detection of colorectal cancer risk. Mutagenesis. 2014;29:221–5. https://doi.org/10.1093/mutage/geu007.
Main PAE, Thomas P, Angley MT, et al. Lack of evidence for genomic instability in autistic children as measured by the cytokinesis-block micronucleus cytome assay. Autism Res. 2015;8:94–104. https://doi.org/10.1002/aur.1428.
Maluf SW, Mergener M, Dalcanale L, et al. DNA damage in peripheral blood of patients with chronic obstructive pulmonary disease (COPD). Mutat Res Toxicol Environ Mutagen. 2007;626:180–4. https://doi.org/10.1016/J.MRGENTOX.2006.10.002.
Manno M, Viau C, Cocker J, et al. Biomonitoring for occupational health risk assessment (BOHRA). Toxicol Lett. 2010;192:3–16. https://doi.org/10.1016/J.TOXLET.2009.05.001.
Martínez-Pérez LM, Cerda-Flores RM, Gallegos-Cabriales EC, et al. Frequency of micronuclei in Mexicans with type 2 diabetes mellitus. Prague Med Rep. 2007;108:248–55.
Migliore L, Coppedè F, Fenech M, Thomas P. Association of micronucleus frequency with neurodegenerative diseases. Mutagenesis. 2011;26:85–92. https://doi.org/10.1093/mutage/geq067.
Najafzadeh M, Normington C, Jacob BK, et al. DNA damage in healthy individuals and respiratory patients after treating whole blood in vitro with the bulk and nano forms of NSAIDs. Front Mol Biosci. 2016;3:50. https://doi.org/10.3389/fmolb.2016.00050.
Palazzo RP, Bagatini PB, Schefer PB, et al. Genomic instability in patients with type 2 diabetes mellitus on hemodialysis. Rev Bras Hematol Hemoter. 2012;34:31–5. https://doi.org/10.5581/1516-8484.20120011.
Petrozzi L, Lucetti C, Scarpato R, et al. Cytogenetic alterations in lymphocytes of Alzheimer’s disease and Parkinson’s disease patients. Neurol Sci. 2002;23:s97–8. https://doi.org/10.1007/s100720200087.
Prasad M, Bronson SC, Warrier T, et al. Evaluation of DNA damage in Type 2 diabetes mellitus patients with and without peripheral neuropathy: a study in South Indian population. J Nat Sci Biol Med. 2015;6:80–4. https://doi.org/10.4103/0976-9668.149096.
Quintana-Sosa M, León-Mejía G, Luna-Carrascal J, et al. Cytokinesis-block micronucleus cytome (CBMN-CYT) assay biomarkers and telomere length analysis in relation to inorganic elements in individuals exposed to welding fumes. Ecotoxicol Environ Saf. 2021;212:111935. https://doi.org/10.1016/j.ecoenv.2021.111935.
Roberts JR, Karr CJ, Health COE. Pesticide exposure in children. Pediatrics. 2012;130:e1765–88. https://doi.org/10.1542/peds.2012-2758.
Rohr P, Kvitko K, da Silva FR, et al. Genetic and oxidative damage of peripheral blood lymphocytes in workers with occupational exposure to coal. Mutat Res. 2013;758:23–8. https://doi.org/10.1016/j.mrgentox.2013.08.006.
Salimi M, Broumand B, Mozdarani H. Association of elevated frequency of micronuclei in peripheral blood lymphocytes of type 2 diabetes patients with nephropathy complications. Mutagenesis. 2016;31:627–33. https://doi.org/10.1093/mutage/gew029.
Santos RA, Teixeira AC, Mayorano MB, et al. DNA repair genes XRCC1 and XRCC3 polymorphisms and their relationship with the level of micronuclei in breast cancer patients. Genet Mol Biol. 2010;33:637–40. https://doi.org/10.1590/S1415-47572010005000082.
Santovito A, Gendusa C. Micronuclei frequency in peripheral blood lymphocytes of healthy subjects living in Turin (North-Italy): contribution of body mass index, age and sex. Ann Hum Biol. 2020;47:48–54. https://doi.org/10.1080/03014460.2020.1714728.
Setayesh T, Nersesyan A, Kundi M, et al. Impact of infections, preneoplasia and cancer on micronucleus formation in urothelial and cervical cells: a systematic review. Mutat Res. 2021;787:108361. https://doi.org/10.1016/J.MRREV.2020.108361.
Sordo M, Maciel-Ruiz JA, Salazar AM, et al. Particulate matter-associated micronuclei frequencies in maternal and cord blood lymphocytes. Environ Mol Mutagen. 2019;60:421–7. https://doi.org/10.1002/em.22275.
Sram RJ, Svecova V, Rossnerova A. 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. 2016;770:162–9. https://doi.org/10.1016/J.MRREV.2016.07.009.
Stopper H, Bankoglu EE, Marcos R, Pastor S. Micronucleus frequency in chronic kidney disease patients: a review. Mutat Res. 2020;786:108340. https://doi.org/10.1016/J.MRREV.2020.108340.
Varga D, Johannes T, Jainta S, et al. An automated scoring procedure for the micronucleus test by image analysis. Mutagenesis. 2004;19:391–7. https://doi.org/10.1093/mutage/geh047.
Wagner KH, Schwingshackl L, Draxler A, Franzke B. Impact of dietary and lifestyle interventions in elderly or people diagnosed with diabetes, metabolic disorders, cardiovascular disease, cancer and micronutrient deficiency on micronuclei frequency-a systematic review and meta-analysis. Mutat Res. 2021;787:108367. https://doi.org/10.1016/J.MRREV.2021.108367.
Wang RC, Yang L, Tang Y, Bai O. Micronucleus expression and acute leukemia prognosis. Asian Pac J Cancer Prev. 2013;14:5257–61. https://doi.org/10.7314/APJCP.2013.14.9.5257.
Xavier LA da C, Bezerra JF, de Rezende AA, et al (2017) Analysis of genome instability biomarkers in children with non-syndromic orofacial clefts. Mutagenesis 32:313–321. https://doi.org/10.1093/mutage/gew068.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2023 Springer Nature Switzerland AG
About this entry
Cite this entry
Da Silva, J. et al. (2023). Micronucleus Assay in Lymphocytes for Human Biomonitoring and Clinical Studies. In: Patel, V.B., Preedy, V.R., Rajendram, R. (eds) Biomarkers in Toxicology. Biomarkers in Disease: Methods, Discoveries and Applications. Springer, Cham. https://doi.org/10.1007/978-3-031-07392-2_40
Download citation
DOI: https://doi.org/10.1007/978-3-031-07392-2_40
Published:
Publisher Name: Springer, Cham
Print ISBN: 978-3-031-07391-5
Online ISBN: 978-3-031-07392-2
eBook Packages: Biomedical and Life SciencesReference Module Biomedical and Life Sciences