Chromosomal rearrangements involving telomeric DNA sequences in Balb/3T3 cells transfected with the Ha-ras oncogene.
Chromosomal instability involving telomeric DNA sequences was studied in mouse Balb/3T3 fibroblasts transfected with a mutated human c-Ha-ras-1 gene (B61 cells) and spontaneously immortalized normal parental cells (A31 cells), using fluorescence in situ hybridization (FISH). FISH analysis with a telomeric probe revealed high frequencies of chromosome alterations involving telomeric regions, mainly stable and unstable Robertsonian fusion-like configurations (RLC) (0.25 and 1.95/cell in A31 and B61 cells, respectively) and chromosome ends lacking telomeric signals in one (LTS') or both chromatids (LTS") (5.9 and 17.5/cell for A31 and B61 cells, respectively). Interstitial telomeric sequences (ITS) were also detected at both non-telomeric sites and in the centromeres of RLC. The frequencies of RLCs with ITS located in the centromeres were 3-fold higher in B61 compared with A31 cells. We demonstrated a high level of chromosome instability involving telomeric DNA sequences in ras-transfected cells overexpressing ras mRNA, which could be a consequence of rapid cell cycle progression associated with a deficient telomere capping mechanism.
Peitl
Paulo
P
Departamento de Genética, Faculdade de Medicina, Universidade de São Paulo, Campus de Ribeirão Preto, SP, Brasil.
Mello
Stephano S
SS
Camparoto
Marjori L
ML
Passos
Geraldo A S
GA
Hande
Manoor P
MP
Cardoso
Renato S
RS
Sakamoto-Hojo
Elza T
ET
D000818:Animals; D002453:Cell Cycle / Q000235:genetics; D002461:Cell Line, Transformed; D002869:Chromosome Aberrations; D002875:Chromosomes / Q000235:genetics / Q000648:ultrastructure*; D004247:DNA / Q000235:genetics; D005347:Fibroblasts / Q000648:ultrastructure*; D011905:Genes, ras; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D051379:Mice; D008807:Mice, Inbred BALB C; D016283:Proto-Oncogene Proteins p21(ras) / Q000502:physiology*; D012333:RNA, Messenger / Q000096:biosynthesis; D011993:Recombinant Fusion Proteins / Q000502:physiology; D016615:Telomere / Q000648:ultrastructure*; D014162:Transfection; D014178:Translocation, Genetic
D012333:RNA, Messenger; D011993:Recombinant Fusion Proteins; D004247:DNA; C501009:HRAS protein, human; D016283:Proto-Oncogene Proteins p21(ras)