P53 oncosuppressor influences selection of genomic imbalances in response to ionizing radiations in human osteosarcoma cell line SAOS-2.
OBJECTIVE
To investigate the impact of TP53 (tumor protein 53, p53) on genomic stability of osteosarcoma (OS).


METHODS
In first instance, we expressed in OS cell line SAOS-2 (lacking p53) a wild type (wt) p53 construct, whose protein undergoes nuclear import and activation in response to ionizing radiations (IR). Thereafter, we investigated genomic imbalances (amplifications and deletions at genes or DNA regions most frequently altered in human cancers) associated with radio-resistance relative to p53 expression by mean of an array-based comparative genomic hybridization (aCGH) strategy. Finally we investigated a putative marker of radio-induced oxidative stress, a 4,977 bp deletion at mitochondrial (mt) DNA usually referred to as 'common' deletion, by mean of a polimerase chain reaction (PCR) strategy.


RESULTS
In radio-resistant subclones generated from wt p53-transfected SAOS-2 cells DNA deletions were remarkably reduced and the accumulation of 'common' deletion at mtDNA (that may let the persistence of oxidative damage by precluding detoxification from reactive oxygen species [ROS]) completely abrogated.


CONCLUSIONS
The results of our study confirm that wt p53 has a role in protection of OS cell DNA integrity. Multiple mechanisms involved in p53 safeguard of genomic integrity and prevention of deletion outcome are discussed.
Zuffa
Elisa
E
Department of Radiation Oncology Luigi Galvani, University of Bologna-Medical School, Bologna, Italy. ELYZ79@libero.it
Mancini
Manuela
M
Brusa
Gianluca
G
Pagnotta
Eleonora
E
Hattinger
Claudia Maria
CM
Serra
Massimo
M
Remondini
Daniel
D
Castellani
Gastone
G
Corrado
Patrizia
P
Barbieri
Enza
E
Santucci
Maria Alessandra
MA
D045744:Cell Line, Tumor; D004272:DNA, Mitochondrial / Q000378:metabolism / Q000528:radiation effects*; D042822:Genomic Instability / Q000235:genetics / Q000502:physiology / Q000528:radiation effects*; D006801:Humans; D009693:Nucleic Acid Hybridization; D020411:Oligonucleotide Array Sequence Analysis; D010006:Osteoblasts / Q000166:cytology / Q000502:physiology / Q000528:radiation effects*; D012516:Osteosarcoma / Q000235:genetics / Q000473:pathology; D011839:Radiation, Ionizing; D017382:Reactive Oxygen Species / Q000378:metabolism / Q000528:radiation effects*; D012641:Selection, Genetic; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism / Q000528:radiation effects*
D004272:DNA, Mitochondrial; D017382:Reactive Oxygen Species; D016159:Tumor Suppressor Protein p53