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

Locate full-text(opens in a new window)|NILDE - Document delivery(opens in a new window)|View at Publisher| Export | Download | Add to List | More... Environmental and Molecular Mutagenesis Volume 49, Issue 6, July 2008, Pages 467-475 Chromosome aberrations and telomere length modulation in bone marrow and spleen cells of melphalan-treated p53+/- mice (Article) Sgura, A.ad , De Amicis, A.a, Stronati, L.b, Cinelli, S.c, Pacchierotti, F.b, Tanzarella, C.a a Department of Biology, University Roma Tre, Rome, Italy b Section of Toxicology and Biomedical Sciences, ENEA CR Casaccia, Rome, Italy c Research Toxicology Center, Pomezia, Italy View additional affiliations View references (70) 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.