Molecular mechanisms by which in vivo exposure to exogenous chemical genotoxic agents can lead to micronucleus formation in lymphocytes in vivo and ex vivo in humans

Mutation Research - Reviews in Mutation Research

Volumn 770, Issue , 2016, Pages 12-25

  Fenech, Michael ^a   Knasmueller, Siegfried ^b   Bolognesi, Claudia ^c   Bonassi, Stefano ^d   Holland, Nina ^e   Migliore, Lucia ^f   Palitti, Fabrizio ^g   Natarajan, Adayapalam T ^g   Kirsch Volders, Micheline ^h  

^a CSIRO   (Australia)

^b MEDICAL UNIVERSITY OF VIENNA   (Austria)

^c UNIVERSITY OF GENOA   (Italy)

^d IRCCS SAN RAFFAELE PISANA   (Italy)

^e UNIVERSITY OF CALIFORNIA   (United States)

^f UNIVERSITY OF PISA   (Italy)

^g UNIVERSITY OF TUSCIA   (Italy)

^h VRIJE UNIVERSITEIT BRUSSEL   (Belgium)

Author keywords

Chemical; Ex vivo; Exogenous; Exposure; Genotoxins; Humans; In vivo; Lymphocytes; Mechanisms; Micronucleus; Molecular

Indexed keywords

CHEMICAL AGENT; TOXIN; MUTAGENIC AGENT;

CELL KINETICS; CENTROMERE; CHROMOSOME; CROSS LINKING; CYTOKINESIS; DNA DAMAGE; DNA STRAND BREAKAGE; EX VIVO STUDY; GENOTOXICITY; HUMAN; IN VIVO STUDY; LYMPHOCYTE; MICRONUCLEUS; PRIORITY JOURNAL; REVIEW; DNA REPAIR; DRUG EFFECTS; IN VITRO STUDY; ULTRASTRUCTURE;

DNA DAMAGE; DNA REPAIR; HUMANS; IN VITRO TECHNIQUES; LYMPHOCYTES; MICRONUCLEI, CHROMOSOME-DEFECTIVE; MUTAGENS;

EID: 84999683541     PISSN: 13835742     EISSN: 13882139     Source Type: Journal    
DOI: 10.1016/j.mrrev.2016.04.008     Document Type: Review

References (83)

1. [1] Fenech, M., Holland, N., Zeiger, E., Chang, W.P., Burgaz, S., Thomas, P., Bolognesi, C., Knasmueller, S., Kirsch-Volders, M., Bonassi, S., The HUMN and HUMNxL international collaboration projects on human micronucleus assays in lymphocytes and buccal cells–past, present and future. Mutagenesis 26:Jan (1) (2011), 239–245.
2. [2] Fenech, M., Cytokinesis-block micronucleus cytome assay. Nat. Protoc. 2:5 (2007), 1084–1104.
3. [3] Fenech, M., Kirsch-Volders, M., Natarajan, A.T., Surralles, J., Crott, J.W., Parry, J., Norppa, H., Eastmond, D.A., Tucker, J.D., Thomas, P., Molecular mechanisms of micronucleus, nucleoplasmic bridge and nuclear bud formation in mammalian and human cells. Mutagenesis 26:Jan (1) (2011), 125–132.
4. [4] Kirsch-Volders, M., Vanhauwaert, A., De Boeck, M., Decordier, I., Importance of detecting numerical versus structural chromosome aberrations. Mutat. Res. 504:Jul 25 (1–2) (2002), 137–148.
5. [5] OECD guideline for testing of chemicals (2010) in vitro micronucleus test 487. In vitro mammalian micronucleus test (MNVIT). Organisation for Economic Cooperation and Development, Paris.
6. [6] Russo, A., Pacchierotti, F., Cimini, D., Ganem, N.J., Genescà, A., Natarajan, A.T., Pavanello, S., Valle, G., Degrassi, F., Genomic instability: crossing pathways at the origin of structural and numerical chromosome changes. Environ. Mol. Mutagen. 56:Mar (18) (2015), 563–580.
7. [7] Durante, M., Bedford, J.S., Chen, D.J., Conrad, S., Cornforth, M.N., Natarajan, A.T., van Gent, D.C., Obe, G., From DNA damage to chromosome aberrations: joining the break. Mutat. Res. 756:Aug 30 (1–2) (2013), 5–13.
8. [8] Fenech, M., The lymphocyte cytokinesis-block micronucleus cytome assay and its application in radiation biodosimetry. Health Phys. 98:Feb (2) (2010), 234–243.
9. [9] Purton L.E., Scadden D.T., The hematopoietic stem cell niche. 2008 Nov 15. StemBook [Internet]. Cambridge (MA): Harvard Stem Cell Institute; 2008. Available from http://www.ncbi.nlm.nih.gov/books/NBK27051/ PubMed PMID: 20614611.
10. [10] O'Malley, D.P., Kim, Y.S., Perkins, S.L., Baldridge, L., Juliar, B.E., Orazi, A., Morphologic and immunohistochemical evaluation of splenic hematopoietic proliferations in neoplastic and benign disorders. Mod. Pathol. 18 (2005), 1550–1561.
11. [11] Odagiri, Y., Takemoto, K., Fenech, M., Micronucleus induction in cytokinesis-blocked mouse bone marrow cells in vitro following in vivo exposure to X-irradiation and cyclophosphamide. Environ. Mol. Mutagen. 24:1 (1994), 61–67.
12. [12] Aguilera, A., Gómez-González, B., Genome instability: a mechanistic view of its causes and consequences. Nat. Rev. Genet. 9:Mar (3) (2008), 204–217.
13. [13] Gelot, C., Magdalou, I., Lopez, B.S., Replication stress in Mammalian cells and its consequences for mitosis. Genes (Basel) 6:May 22 (2) (2015), 267–298.
14. [14] Kaufmann, J.M., Hodgkin, G.R., Lewin, P.D., Kelleher, S.R., Davenport, A.D., Zaunders, M.P., Naive T cells are maintained by thymic output in early ages but by proliferation without phenotypic change after age twenty. Immunol. Cell Biol. 81:Dec (6) (2003), 487–495.
15. [15] Michie, C.A., McLean, A., Alcock, C., Beverley, P.C., Lifespan of human lymphocyte subsets defined by CD45 isoforms. Nature 360:Nov 19 (6401) (1992), 264–265.
16. [16] Weng, H., Morimoto, K., Differential responses to mutagens among human lymphocyte subpopulations. Mutat. Res. 672:Jan (1) (2009), 1–9.
17. [17] Högstedt, B., Karlsson, A., Bratt, I., Holmén, A., Micronucleus induction in human B and T lymphocytes separated by an immunomagnetic technique. Hereditas 119:2 (1993), 99–103.
18. [18] Anglin, E.J., Salisbury, C., Bailey, S., Hor, M., Macardle, P., Fenech, M., Thissen, H., Voelcker, N.H., Sorted cell microarrays as platforms for high-content informational bioassays. Lab. Chip 10:Dec 21 (24) (2010), 3413–3421.
19. [19] Panousis, C., Kettle, A.J., Phillips, D.R., Neutrophil-mediated activation of mitoxantrone to metabolites which form adducts with DNA. Cancer Lett. 113:Feb 26 (1–2) (1997), 173–178.
20. [20] Umegaki, K., Fenech, M., Cytokinesis-block micronucleus assay in WIL2-NS cells: a sensitive system to detect chromosomal damage induced by reactive oxygen species and activated human neutrophils. Mutagenesis 15:May (3) (2000), 261–269.
21. [21] Borm, P.J., Tran, L., Donaldson, K., The carcinogenic action of crystalline silica: a review of the evidence supporting secondary inflammation-driven genotoxicity as a principal mechanism. Crit. Rev. Toxicol. 41:Oct (9) (2011), 756–770.
22. [22] Knaapen, A.M., Güngör, N., Schins, R.P., Borm, P.J., Van Schooten, F.J., Neutrophils and respiratory tract DNA damage and mutagenesis: a review. Mutagenesis 21:Jul (4) (2006), 225–236.
23. [23] Sapkota, M., Wyatt, T.A., Alcohol, aldehydes, adducts and airways. Biomolecules 5:Nov 5 (4) (2015), 2987–3008.
24. [24] Donaldson, K., Brown, G.M., Brown, D.M., Bolton, R.E., Davis, J.M., Inflammation generating potential of long and short fibre amosite asbestos samples. Br. J. Ind. Med. 46:Apr (4) (1989), 271–276.
25. [25] Murta, G.L., Campos, K.K., Bandeira, A.C., Diniz, M.F., de Paula Costa, G., Costa, D.C., Talvani, A., Lima, W.G., Bezerra, F.S., Oxidative effects on lung inflammatory response in rats exposed to different concentrations of formaldehyde. Environ. Pollut. 14:Jan (211) (2016), 206–213.
26. [26] Pampalona, J., Soler, D., Genesca’, A., Tusell, L., Telomere dysfunction and chromosome structure modulate the contribution of individual chromosomes in abnormal nuclear morphologies. Mutat. Res. 683 (2010), 16–22.
27. [27] Utani, K., Kohno, Y., Okamoto, A., Shimizu, N., Emergence of micronuclei and their effects on the fate of cells under replication stress. PLoS One, 5, 2010, e10089.
28. [28] Bender, M.A., Griggs, H.G., Bedford, J.S., Mechanisms of chromosomal aberration production. 3. Chemicals and ionizing radiation. Mutat. Res. 23:May (2) (1974), 197–212.
29. [29] Bender, M.A., Griggs, H.G., Walker, P.L., Mechanisms of chromosomal aberration production. I. Aberration induction by ultraviolet light. Mutat Res. 20:Dec (3) (1973), 387–402.
30. [30] Brewen, J.G., Stetka, D.G., Cytogenetic events in vivo. Mutagenicity: New Horizons in Genetic Toxicology, 1982, Academic Press, 351–384.
31. [31] Natarajan, A.T., Chromosome aberrations: past, present and future. Mutat. Res. 504:Jul 25 (1–2) (2002), 3–16.
32. [32] Savage, J.R., On the nature of visible chromosomal gaps and breaks. Cytogenet. Genome Res. 104:1–4 (2004), 46–55.
33. [33] Savage, J.R.K., Micronuclei: Pitfalls and Problems. Atlas Genet Cytogenet Oncol Haematol. 2004 http://AtlasGeneticsOncology.org/Deep/MicronucleiID20016.html.
34. [34] Takahashi, A., Ohnishi, T., Does gammaH2AX foci formation depend on the presence of DNA double strand breaks?. Cancer Lett. 229:Nov 18 (2) (2005), 171–179.
35. [35] Smart, D.J., Ahmedi, K.P., Harvey, J.S., Lynch, A.M., Genotoxicity screening via the γH2AX by flow assay. Mutat. Res. 715:Oct 1 (1–2) (2011), 25–31.
36. [36] Parry, J.M., Parry, E.M., The use of the in vitro micronucleus assay to detect and assess the aneugenic activity of chemicals. Mutat. Res. 607:Aug 4 (1) (2006), 5–8.
37. [37] Kirsch-Volders, M., Plas, G., Elhajouji, A., Lukamowicz, M., Gonzalez, L., Vande Loock, K., Decordier, I., The in vitro MN assay in 2011: origin and fate, biological significance, protocols, high throughput methodologies and toxicological relevance. Arch. Toxicol. 85:Aug (8) (2011), 873–899.
38. [38] Luzhna, L., Kathiria, P., Kovalchuk, O., Micronuclei in genotoxicity assessment: from genetics to epigenetics. Front. Genet. 4:131 (2013), 1–17.
39. [39] Fenech, M., Folate (vitamin B9) and vitamin B12 and their function in the maintenance of nuclear and mitochondrial genome integrity. Mutat. Res. 733:May 1 (1–2) (2012), 21–33.
40. [40] Ramırez, T., Stopper, H., Hockd, R., Herrera, L.A., Prevention of aneuploidy by S-adenosyl-methionine in human cells treated with sodium arsenite. Mutat. Res. 617 (2007), 16–22.
41. [41] Guttenbach, M., Schmid, M., Exclusion of specific human chromosomes into micronuclei by 5-azacytidine treatment of lymphocyte cultures. Exp. Cell Res. 211:Mar (1) (1994), 127–132.
42. [42] Prada, D., González, R., Sánchez, L., Castro, C., Fabián, E., Herrera, L.A., Satellite 2 demethylation induced by 5-azacytidine is associated with missegregation of chromosomes 1 and 16 in human somatic cells. Mutat. Res. 729:Jan 3 (1–2) (2012), 100–105.
43. [43] Leyton, C., Mergudich, D., de la Torre, C., Sans, J., Impaired chromosome segregation in plant anaphase after moderate hypomethylation of DNA. Cell Prolif. 28:Sep (9) (1995), 481–496.
44. [44] Whitwell, J., Fowler, P., Allars, S., Jenner, K., Lloyd, M., Wood, D., Smith, K., Young, J., Jeffrey, L., Kirkland, D., 2-Aminoanthracene, 5-fluorouracil, colchicine, benzo[a]pyrene, cadmium chloride and cytosine arabinoside tested in the in vitro mammalian cell micronucleus test (MNvit) in Chinese hamster ovary (CHO) cells at Covance Laboratories, Harrogate UK in support of OECD draft Test Guideline 487. Mutat. Res. 702:Oct 29 (2) (2010), 237–247, 10.1016/j.mrgentox.2010.05.004 (Epub 2010 May 15).
45. [45] Ladeira, C., Viegas, S., Pádua, M., Gomes, M., Carolino, E., Gomes, M.C., Brito, M., Assessment of genotoxic effects in nurses handling cytostatic drugs. J. Toxicol. Environ. Health (2014) Part A 77:14–16 (2014), 879–887.
46. [46] Watson, R.E., McKim, J.M., Cockerell, G.L., Goodman, J.I., The value of DNA methylation analysis in basic, initial toxicity assessments. Toxicol. Sci. 79:May (1) (2004), 178–188.
47. [47] Mojardín, L., Botet, J., Moreno, S., Salas, M., Chromosome segregation and organization are targets of 5í-Fluorouracil in eukaryotic cells. Cell Cycle 14:2 (2015), 206–218.
48. [48] Rochette, P.J., Brash, D.E., Human telomeres are hypersensitive to UV-induced DNA Damage and refractory to repair. PLoS Genet., 6(Apr 29 (4)), 2010, e1000926.
49. [49] Fumagalli, M., Rossiello, F., Clerici, M., Barozzi, S., Cittaro, D., Kaplunov, J.M., Bucci, G., Dobreva, M., Matti, V., Beausejour, C.M., Herbig, U., Longhese, M.P., d'Adda di Fagagna, F., Telomeric DNA damage is irreparable and causes persistent DNA-damage-response activation. Nat. Cell Biol. 14:Mar 18 (4) (2012), 355–365.
50. [50] Rossiello, F., Herbig, U., Longhese, M.P., Fumagalli, M., d'Adda di Fagagna F. Irrepairable telomeric DNA damage and persistent DDR signalling as a shared causative mechanism of cellular senescence and ageing. Curr. Opin. Genet. Dev. 26:Jun (2014), 89–95.
51. [51] Opresko, P.L., Fan, J., Danzy, S., Wilson, D.M. 3rd, Bohr, V.A., Oxidative damage in telomeric DNA disrupts recognition by TRF1 and TRF2. Nucleic Acids Res. 33:Feb 24 (4) (2005), 1230–1239.
52. [52] Bull, C., Fenech, M., Genome-health nutrigenomics and nutrigenetics: nutritional requirements or ‘nutriomes' for chromosomal stability and telomere maintenance at the individual level. Proc. Nutr. Soc. 67:May (2) (2008), 146–156.
53. [53] Campisi, J., Aging, cellular senescence, and cancer. Annu. Rev. Physiol. 75 (2013), 685–705.
54. [54] Hoffelder, D.R., Luo, L., Burke, N.A., Watkins, S.C., Gollin, S.M., Saunders, W.S., Resolution of anaphase bridges in cancer cells. Chromosoma 112:Jun (8) (2004), 389–397.
55. [55] Fenech, M., Crott, J.W., Micronuclei, nucleoplasmic bridges and nuclear buds induced in folic acid deficient human lymphocytes-evidence for breakage-fusion-bridge cycles in the cytokinesis-block micronucleus assay. Mutat. Res. 504:Jul 25 (1–2) (2002), 131–136.
56. [56] Lindahl, T., Keynote: past, present, and future aspects of base excision repair. Prog. Nucleic Acid Res. Mol. Biol. 68 (2001), xvii–xxx.
57. [57] Krokan, H.E., Bjørås, M., Base excision repair. Cold Spring Harb Perspect Biol., 5(Apr 1 (4)), 2013, a012583, 10.1101/cshperspect.a012583.
58. [58] Robertson, A.B., Klungland, A., Rognes, T., Leiros, I., DNA repair in mammalian cells: base excision repair: the long and short of it. Cell. Mol. Life Sci. 66:Mar (6) (2009), 981–993, 10.1007/s00018-009-8736-z.
59. [59] Marti, T.M., Fleck, O., DNA repair nucleases. Cell. Mol. Life Sci. 61:Feb (3) (2004), 336–354.
60. [60] Dianov, G.L., Timchenko, T.V., Sinitsina, O.I., Kuzminov, A.V., Medvedev, O.A., Salganik, R.I., Repair of uracil residues closely spaced on the opposite strands of plasmid DNA results in double-strand break and deletion formation. Mol. Gen. Genet. 225:Mar (3) (1991), 448–452.
61. [61] Natarajan, A.T., Obe, G., Molecular mechanisms involved in the production of chromosomal aberrations. I. Utilization of Neurospora endonuclease for the study of aberration production in G2 stage of the cell cycle. Mutat. Res. 52:Oct (1) (1978), 137–149.
62. [62] Natarajan, A.T., Obe, G., van Zeeland, A.A., Palitti, F., Meijers, M., Verdegaal-Immerzeel, E.A., Molecular mechanisms involved in the production of chromosomal aberrations. II. Utilization of Neurospora endonuclease for the study of aberration production by X-rays in G1 and G2 stages of the cell cycle. Mutat. Res. 69:Feb (2) (1980), 293–305.
63. [63] Fenech, M., Neville, S., Conversion of excision-repairable DNA lesions to micronuclei within one cell cycle in human lymphocytes. Environ. Mol. Mutagen. 19:1 (1992), 27–36.
64. [64] Fenech, M., Rinaldi, J., Surralles, J., The origin of micronuclei induced by cytosine arabinoside and its synergistic interaction with hydroxyurea in human lymphocytes. Mutagenesis 9:May (3) (1994), 273–277.
65. [65] Leopardi, P., Zijno, A., Marcon, F., Conti, L., Carere, A., Verdina, A., Galati, R., Tomei, F., Baccolo, T.P., Crebelli, R., Analysis of micronuclei in peripheral blood lymphocytes of traffic wardens: effects of exposure, metabolic genotypes, and inhibition of excision repair in vitro by ARA-C. Environ. Mol. Mutagen. 41:2 (2003), 126–130.
66. [66] Zhang, C.Z., Spektor, A., Cornils, H., Francis, J.M., Jackson, E.K., Liu, S., Meyerson, M., Pellman, D., Chromothripsis from DNA damage in micronuclei. Nature(May 27), 2015, 10.1038/nature14493 (Epubaheadofprint).
67. [67] Holland, A.J., Cleveland, D.W., Chromoanagenesis and cancer: mechanisms and consequences of localized, complex chromosomal rearrangements. Nat. Med. 18:Nov (11) (2012), 1630–1638.
68. [68] Okamoto, A., Utani, K., Shimizu, N., DNA replication occurs in all lamina positive micronuclei, but never in lamina negative micronuclei. Mutagenesis 27:May (3) (2012), 323–327.
69. [69] Pihan, G.A., Centrosome dysfunction contributes to chromosome instability, chromoanagenesis, and genome reprograming in cancer. Front. Oncol., 3(Nov 12), 2013, 277, 10.3389/fonc.2013.00277 (eCollection2013).
70. [70] Kirsch-Volders, M., Fenech, M., Inclusion of micronuclei in non-divided mononuclear lymphocytes and necrosis/apoptosis may provide a more comprehensive cytokinesis block micronucleus assay for biomonitoring purposes. Mutagenesis 16:Jan (1) (2001), 51–58.
71. [71] Fenech, M., Perepetskaya, G., Mikhalevich, L., A more comprehensive application of the micronucleus technique for biomonitoring of genetic damage rates in human populations–experiences from the Chernobyl catastrophe. Environ. Mol. Mutagen. 30:2 (1997), 112–118.
72. [72] El-Zein, R.A., Fenech, M., Lopez, M.S., Spitz, M.R., Etzel, C.J., Cytokinesis-blocked micronucleus cytome assay biomarkers identify lung cancer cases amongst smokers. Cancer Epidemiol. Biomarkers Prev. 17:May (5) (2008), 1111–1119.
73. [73] Marini, V., Michelazzi, L., Cioé, A., Fucile, C., Spigno, F., Robbiano, L., Exposure to asbestos: correlation between blood levels of mesothelin and frequency of micronuclei in peripheral blood lymphocytes. Mutat. Res. 721:Mar 18 (1) (2011), 114–117.
74. [74] Bull, C.F., Beetstra-Hill, S., Benassi-Evans, B.J., Crott, J.W., Kimura, M., Teo, T., Wu, J., Fenech, M.F., Application and adaptation of the in vitro micronucleus assay for the assessment of nutritional requirements of cells for DNA damage prevention. Mutagenesis 26:Jan (1) (2011), 193–197.
75. [75] Benassi-Evans, B., Fenech, M., Chronic alcohol exposure induces genome damage measured using the cytokinesis-block micronucleus cytome assay and aneuploidy in human B lymphoblastoid cell lines. Mutagenesis 26:May (3) (2011), 421–429.
76. [76] Kimura, M., Umegaki, K., Higuchi, M., Thomas, P., Fenech, M., Methylenetetrahydrofolate reductase C677 T polymorphism, folic acid and riboflavin are important determinants of genome stability in cultured human lymphocytes. J. Nutr. 134:Jan (1) (2004), 48–56.
77. [77] Bull, C.F., Mayrhofer, G., O'Callaghan, N.J., Au, A.Y., Pickett, H.A., Low, G.K., Zeegers, D., Hande, M.P., Fenech, M.F., Folate deficiency induces dysfunctional long and short telomeres; both states are associated with hypomethylation and DNA damage in human WIL2-NS cells. Cancer Prev. Res. (Phila.) 7:Jan (1) (2014), 128–138.
78. [78] Godderis, L., De Boeck, M., Haufroid, V., Emmery, M., Mateuca, R., Gardinal, S., Kirsch-Volders, M., Veulemans, H., Lison, D., Influence of genetic polymorphisms on biomarkers of exposure and genotoxic effects in styrene-exposed workers. Environ. Mol. Mutagen. 44:4 (2004), 293–303.
79. [79] Ceppi, M., Biasotti, B., Fenech, M., Bonassi, S., population studies with the exfoliated buccal micronucleus assay: statistical and epidemiological issues. Mutat. Res. 705:Jul–Sep (1) (2010), 11–19.
80. [80] Nersesyan, A., Kundi, M., Fenech, M., Bolognesi, C., Misik, M., Wultsch, G., Hartmann, M., Knasmueller, S., Micronucleus assay with urine derived cells (UDC): a review of its application in human studies investigating genotoxin exposure and bladder cancer risk. Mutat. Res. Rev. Mutat. Res. 762:Oct–Dec (2014), 37–51.
81. [81] Mateuca, R., Lombaert, N., Aka, P.V., Decordier, I., Kirsch-Volders, M., Chromosomal changes: induction, detection methods and applicability in human biomonitoring. Biochimie 88:Nov (11) (2006), 1515–1531.
82. [82] Marx, K.A., Zhou, T., Montrone, A., McIntosh, D., Braunhut, S.J., A comparative study ofthe cytoskeleton binding drugs nocodazole and taxol with a mammalian cell quartz crystal microbalance biosensor: different dynamic responses and energydissipation effects. Anal. Biochem. 361:Feb 1 (1) (2007), 77–92.
83. [83] Kirsch-Volders, M., Parry, E.M., Genetic toxicology of mitotic spindle inhibitors used as anticancer drugs. Mutat. Res. 355:Aug 17 (1–2) (1996), 103–128.