caa a22 4500 445853875 CHVBK 20180317145422.0 cr unu---uuuuu 170323e20110801xx s 000 0 eng 10.1007/s00204-011-0691-4 doi (NATIONALLICENCE)springer-10.1007/s00204-011-0691-4 The in vitro MN assay in 2011: origin and fate, biological significance, protocols, high throughput methodologies and toxicological relevance [Elektronische Daten] [Micheline Kirsch-Volders, Gina Plas, Azeddine Elhajouji, Magdalena Lukamowicz, Laetitia Gonzalez, Kim Vande Loock, Ilse Decordier] Micronuclei (MN) are small, extranuclear bodies that arise in dividing cells from acentric chromosome/chromatid fragments or whole chromosomes/chromatids lagging behind in anaphase and are not included in the daughter nuclei at telophase. The mechanisms of MN formation are well understood; their possible postmitotic fate is less evident. The MN assay allows detection of both aneugens and clastogens, shows simplicity of scoring, is widely applicable in different cell types, is internationally validated, has potential for automation and is predictive for cancer. The cytokinesis-block micronucleus assay (CBMN) allows assessment of nucleoplasmic bridges, nuclear buds, cell division inhibition, necrosis and apoptosis and in combination with FISH using centromeric probes, the mechanistic origin of the MN. Therefore, the CBMN test can be considered as a "cytome” assay covering chromosome instability, mitotic dysfunction, cell proliferation and cell death. The toxicological relevance of the MN test is strong: it covers several endpoints, its sensitivity is high, its predictivity for in vivo genotoxicity requires adequate selection of cell lines, its statistical power is increased by the recently available high throughput methodologies, it might become a possible candidate for replacing in vivo testing, it allows good extrapolation for potential limits of exposure or thresholds and it is traceable in experimental in vitro and in vivo systems. Implementation of in vitro MN assays in the test battery for hazard and risk assessment of potential mutagens/carcinogens is therefore fully justified. Springer-Verlag, 2011 Micronuclei nationallicence Cytokinesis-block micronucleus assay nationallicence Genotoxicity nationallicence Kirsch-Volders Micheline Laboratorium voor Cellulaire Genetica, Vrije Universiteit Brussel, Pleinlaan 2, 1050, Brussels, Belgium aut Plas Gina Laboratorium voor Cellulaire Genetica, Vrije Universiteit Brussel, Pleinlaan 2, 1050, Brussels, Belgium aut Elhajouji Azeddine Novartis Institutes for Biomedical Research, Translational Sciences, Preclinical Safety, Genetic Toxicology and Safety Pharmacology, MUT-2881.5.38, 4002, Basel, Switzerland aut Lukamowicz Magdalena Novartis Institutes for Biomedical Research, Translational Sciences, Preclinical Safety, Genetic Toxicology and Safety Pharmacology, MUT-2881.5.38, 4002, Basel, Switzerland aut Gonzalez Laetitia Laboratorium voor Cellulaire Genetica, Vrije Universiteit Brussel, Pleinlaan 2, 1050, Brussels, Belgium aut Vande Loock Kim Laboratorium voor Cellulaire Genetica, Vrije Universiteit Brussel, Pleinlaan 2, 1050, Brussels, Belgium aut Decordier Ilse Laboratorium voor Cellulaire Genetica, Vrije Universiteit Brussel, Pleinlaan 2, 1050, Brussels, Belgium aut Archives of Toxicology Springer-Verlag 85/8(2011-08-01), 873-899 0340-5761 85:8<873 2011 85 204 https://doi.org/10.1007/s00204-011-0691-4 text/html Onlinezugriff via DOI 1 review-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s00204-011-0691-4 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Kirsch-Volders Micheline Laboratorium voor Cellulaire Genetica, Vrije Universiteit Brussel, Pleinlaan 2, 1050, Brussels, Belgium aut NATIONALLICENCE 700 1- Plas Gina Laboratorium voor Cellulaire Genetica, Vrije Universiteit Brussel, Pleinlaan 2, 1050, Brussels, Belgium aut NATIONALLICENCE 700 1- Elhajouji Azeddine Novartis Institutes for Biomedical Research, Translational Sciences, Preclinical Safety, Genetic Toxicology and Safety Pharmacology, MUT-2881.5.38, 4002, Basel, Switzerland aut NATIONALLICENCE 700 1- Lukamowicz Magdalena Novartis Institutes for Biomedical Research, Translational Sciences, Preclinical Safety, Genetic Toxicology and Safety Pharmacology, MUT-2881.5.38, 4002, Basel, Switzerland aut NATIONALLICENCE 700 1- Gonzalez Laetitia Laboratorium voor Cellulaire Genetica, Vrije Universiteit Brussel, Pleinlaan 2, 1050, Brussels, Belgium aut NATIONALLICENCE 700 1- Vande Loock Kim Laboratorium voor Cellulaire Genetica, Vrije Universiteit Brussel, Pleinlaan 2, 1050, Brussels, Belgium aut NATIONALLICENCE 700 1- Decordier Ilse Laboratorium voor Cellulaire Genetica, Vrije Universiteit Brussel, Pleinlaan 2, 1050, Brussels, Belgium aut NATIONALLICENCE 773 0- Archives of Toxicology Springer-Verlag 85/8(2011-08-01), 873-899 0340-5761 85:8<873 2011 85 204 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer