Chromosomal instability and telomere lengths of each chromosomal arm measured by Q-FISH in human fibroblast strains prior to replicative senescence

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 (≧40 PDLs), 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 62 PDL, 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.

Research highlights▶ Q-FISH to measure telomere lengths of p- and q-arms was performed. ▶ Chromosomes with excessively shortened telomeres showed fusions and anaphase bridges. ▶ Fusion and anaphase bridges were observed in diploid fibroblasts in late PDL. ▶ Anaphase bridges were often associated with chromosomes with shortened telomeres. ▶ Anaphase bridges were often associated with chromosomes X and/or 21.