title: Chromosomal instability and telomere lengths of each chromosomal arm measured by Q-FISH in human fibroblast strains prior to replicative senescence.
abstract: We monitored the telomere lengths and chromosomal instability characteristics of fibroblasts at different population doubling levels (PDLs) to gain further insight into the role of telomere shortening in chromosomal instability. We used 7 normal diploid human fibroblast strains (TIG-1, 3, 7, 103, 104, 112, and 114) and a quantitative fluorescence in situ hybridization method to measure telomere lengths of the p- and q-arms of individual chromosomes. We also enumerated morphologic signs of chromosomal instability, including fusion or loss of chromosomes, and anaphase bridges. In strains TIG-1, 3, 7, 103, and 114 at the late (phase 3) stage (≧40PDLs), 29 (96.6%) of 30 fusions were associated with one or both of the chromosomal arms that bear significantly shorter telomeres in those populations. In TIG-1 at 62PDL, 6 fusions were associated with Xq (n=3), 21q (n=3), and other (n=6) chromosomes. Xq and 21q had significantly shorter telomeres, and anaphase bridges were often associated with chromosomes X and/or 21 (74.6%). Our results indicate that chromosomes having excessively shortened telomeres at late PDLs begin to show features of instability such as fusions and anaphase bridges.
authors.affiliation: Research Team for Geriatric Pathology, Tokyo Metropolitan Institute of Gerontology, Itabashi-ku, Tokyo, Japan. takubo@tmig.or.jp
authors.forename: Kaiyo
authors.initials: K
authors.lastname: Takubo
authors.forename: Junko
authors.initials: J
authors.lastname: Aida
authors.forename: Naotaka
authors.initials: N
authors.lastname: Izumiyama
authors.forename: Naoshi
authors.initials: N
authors.lastname: Ishikawa
authors.forename: Mutsunori
authors.initials: M
authors.lastname: Fujiwara
authors.forename: Steven S S
authors.initials: SS
authors.lastname: Poon
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kondo
authors.forename: Makoto
authors.initials: M
authors.lastname: Kammori
authors.forename: Masaaki
authors.initials: M
authors.lastname: Matsuura
authors.forename: Motoji
authors.initials: M
authors.lastname: Sawabe
authors.forename: Tomio
authors.initials: T
authors.lastname: Arai
authors.forename: Duncan M
authors.initials: DM
authors.lastname: Baird
authors.forename: Ken-Ichi
authors.initials: K
authors.lastname: Nakamura
mesh_terms: D000328:Adult; D000368:Aged; D000705:Anaphase / Q000502:physiology; D002460:Cell Line; D016922:Cellular Senescence / Q000502:physiology*; D043171:Chromosomal Instability; D002891:Chromosomes, Human, Pair 21 / Q000235:genetics / Q000378:metabolism*; D041321:Chromosomes, Human, X / Q000235:genetics / Q000378:metabolism*; D005260:Female; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D016615:Telomere / Q000235:genetics / Q000378:metabolism*