Application of chromosome painting and Q-FISH to test the interaction between telomeres and p53 protein in chromosomal aberration induction after Melphalan treatment in p53 +/- mice.

Chromosomal aberrations are a measure of genomic instability, which is known to play a key role in the initiation and promotion of carcinogenesis. Stable reciprocal translocations are of particular importance since they are often involved in neoplastic transformation and tumor cell clonal evolution. Chromosome painting represents a versatile tool in the cytogenetic evaluation of historical and chronic exposure because it can be used for a quick and easy detection of stable genetic damage which persists through cell division. In this study, chromosome painting analysis for chromosome 2 and 7 was used, to test for stable aberrations induced in the bone marrow of wild type and p53+/- C57BL/6J mice exposed for 4 and 13 weeks to 2 mg/kg of melphalan (MLP), a chemotherapeutic agent with carcinogenic potential. Preliminary results indicate that MLP induced comparable levels of chromosome-type aberrations in bone marrow cells of both mouse strains of C57BL/6J mice while a different chromosome aberration frequency after 4 or 13 weeks of treatment was observed.Telomeres stabilize chromosomes and play an important role in tumor development. It is well known that short telomeres are frequently involved in chromosome aberration formation. Furthermore, it has shown that mice without telomerase and with short telomeres are prone to carcinogenesis, and this can be enhanced by deficient checkpoints mediated by p53. In order to understand the involvement of telomere length in chromosome instability and at the same time the role of p53 in the cellular response to telomere dysfunction, in both treated and untreated mice, we are studying telomere length by quantitative fluorescence in situ hybridization (Q-FISH) analysis in both wild-type and p53+/- mice.