title: Live cell imaging of micronucleus formation and development.
abstract: The micronucleus (MN) test is widely used to biomonitor humans exposed to clastogens and aneugens, but little is known about MN development. Here we used confocal time-lapse imaging and a fluorescent human lymphoblastoid cell line (T105GTCH), in which histone H3 and α-tubulin stained differentially, to record the emergence and behavior of micronuclei (MNi) in cells exposed to MN-inducing agents. In mitomycin C (MMC)-treated cells, MNi originated in early anaphase from lagging chromosome fragments just after chromosome segregation. In γ-ray-treated cells showing multipolar cell division, MN originated in late anaphase from lagging chromosome fragments generated by the abnormal cell division associated with supernumerary centrosomes. In vincristine(VC)-treated cells, MN formation was similar to that in MMC-treated cells, but MNi were also derived from whole chromosomes that did not align properly on the metaphase plate. Thus, the MN formation process induced by MMC, γ-rays, and VC, were strikingly different, suggesting that different mechanisms were involved. MN stability, however, was similar regardless of the treatment and unrelated to MN formation mechanisms. MNi were stable in daughter cells, and MN-harboring cells tended to die during cell cycle progression with greater frequency than cells without MN. Because of their persistence, MN may have significant impact on cells, causing genomic instability and abnormally transcribed genes.
authors.affiliation: Division of Genetics and Mutagenesis, National Institute of Health Sciences, Tokyo 158-8501, Japan. m-yasui@nihs.go.jp
authors.forename: Manabu
authors.initials: M
authors.lastname: Yasui
authors.forename: Naoki
authors.initials: N
authors.lastname: Koyama
authors.forename: Tomoko
authors.initials: T
authors.lastname: Koizumi
authors.forename: Kaori
authors.initials: K
authors.lastname: Senda-Murata
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Takashima
authors.forename: Makoto
authors.initials: M
authors.lastname: Hayashi
authors.forename: Kenji
authors.initials: K
authors.lastname: Sugimoto
authors.forename: Masamitsu
authors.initials: M
authors.lastname: Honma
mesh_terms: D002455:Cell Division; D002460:Cell Line; D005453:Fluorescence; D005720:Gamma Rays; D006801:Humans; D048629:Micronuclei, Chromosome-Defective; D015162:Micronucleus Tests / Q000379:methods*; D009153:Mutagens / Q000494:pharmacology
chemical_list: D009153:Mutagens