Chromosome aberrations and telomere length modulation in bone marrow and spleen cells of melphalan-treated p53+/- mice

Antonella Sgura, Andrea De Amicis, Laura Stronati, Serena Cinelli, Francesco Pacchierotti, Caterina Tanzarella

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Abstract

The p53 gene regulates cell cycle and apoptotic pathways after induction of DNA damage. Telomeres, capping chromosome ends, are involved in maintaining chromosome stability; alterations of their length have been related to increased levels of chromosomal aberrations. To study a possible interaction between chromosome aberrations, telomere dysfunction, and p53, we investigated via painting analysis the induction and persistence of chromosome aberrations in bone marrow and spleen cells of p53+/- (and wild type) mice exposed for 4, 13, or 26 weeks to 2 mg/kg melphalan (MLP), a chemotherapeutic agent with carcinogenic potential. In addition, telomere length was evaluated in bone marrow cells by quantitative fluorescence in situ hybridization (Q-FISH). Chromosome aberrations were significantly increased in both tissues after MLP treatment. The p53 genotype did not influence the response of spleen cells, whereas a slight but significant increase of the aberration frequency was measured in the bone marrow of p53+/- mice exposed to MLP for 13 weeks with respect to the level detected in the matched wild-type group. The main finding of our still preliminary results on telomere length modulation was again a difference between the two genotypes. In bone marrow cells of wild-type mice, MLP treatment was associated with telomere shortening, while in p53+/- mice telomere elongation was the prevalent response to MLP exposure. In agreement with previous literature data, our in vivo study suggests that even the lack of a single functional copy of the p53 gene might have an impact on the quantity and quality of chromosome alterations induced in cycling cells by a clastogenic exposure. © 2008 Wiley-Liss, Inc.
Original languageEnglish
Pages (from-to)467 - 475
Number of pages9
JournalEnvironmental and Molecular Mutagenesis
Volume49
Issue number6
DOIs
Publication statusPublished - Jul 2008
Externally publishedYes

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All Science Journal Classification (ASJC) codes

  • Epidemiology
  • Genetics(clinical)
  • Health, Toxicology and Mutagenesis

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