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

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.

• Authors: Antonella Sgura, Andrea De Amicis, Laura Stronati, Serena Cinelli, Francesca Pacchierotti, Caterina Tanzarella
• Journal: Environmental and molecular mutagenesis (Environ Mol Mutagen) Vol. 49 Issue 6 Pg. 467-75 (Jul 2008) ISSN: 1098-2280 [Electronic] United States
• PMID: 18481314 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents, Alkylating
• Tumor Suppressor Protein p53
• Melphalan

Topics

• Animals
• Antineoplastic Agents, Alkylating (toxicity)
• Bone Marrow Cells (cytology, drug effects, metabolism)
• Cells, Cultured
• Chromosome Aberrations (chemically induced)
• Chromosome Painting
• Female
• Genotype
• In Situ Hybridization, Fluorescence (methods)
• Melphalan (toxicity)
• Mice
• Mice, Inbred C57BL
• Mice, Knockout
• Spleen (cytology, drug effects, metabolism)
• Telomere (drug effects, genetics)
• Tumor Suppressor Protein p53 (genetics, physiology)