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Mutagenesis, Vol. 17, No. 1, 67-72, January 2002
© 2002 UK Environmental Mutagen Society/Oxford University Press

Chromosomal rearrangements involving telomeric DNA sequences in Balb/3T3 cells transfected with the Ha-ras oncogene

Paulo Peitl1,*, Stephano S. Mello1,2,*, Marjori L. Camparoto1, Geraldo A.S. Passos1,3, Manoor P. Hande4, Renato S. Cardoso1 and Elza T. Sakamoto-Hojo1,2,5

1 Departamento de Genética, Faculdade de Medicina, 2 Departamento de Biologia, Faculdade de Filosofia, Ciências e Letras and 3 Grupo de Imunogenética Molecular, Departamento de Genética and Faculdade de Odontologia, Universidade de São Paulo, Campus de Ribeirão Preto, SP, Brasil and 4 Center for Radiological Research, Columbia University, New York, NY, USA

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.

* These authors contributed equally to this paper.

5 To whom correspondence should be addressed at: Departmento de Biologia, FFCLRP-usp, Avenida Bandeirantes 3900, 14040-901 Ribeirão Preto, SP, Brasil. Tel: +55 16 602 3827; Fax: =55 16 633 0069: Email: etshojo{at}usp.br


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