Chromosome aberrations and telomere length modulation in bone marrow and spleen cells of melphalan-treated p53+/- mice.
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.
Sgura
Antonella
A
Department of Biology, University Roma Tre, Rome, Italy. sgura@uniroma3.it
De Amicis
Andrea
A
Stronati
Laura
L
Cinelli
Serena
S
Pacchierotti
Francesca
F
Tanzarella
Caterina
C
D000818:Animals; D018906:Antineoplastic Agents, Alkylating / Q000633:toxicity; D001854:Bone Marrow Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D002478:Cells, Cultured; D002869:Chromosome Aberrations / Q000139:chemically induced*; D020223:Chromosome Painting; D005260:Female; D005838:Genotype; D017404:In Situ Hybridization, Fluorescence / Q000379:methods; D008558:Melphalan / Q000633:toxicity*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D013154:Spleen / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D016615:Telomere / Q000187:drug effects* / Q000235:genetics; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000502:physiology*
D018906:Antineoplastic Agents, Alkylating; D016159:Tumor Suppressor Protein p53; D008558:Melphalan