P53 oncosuppressor influences selection of genomic imbalances in response to ionizing radiations in human osteosarcoma cell line SAOS-2

Elisa Zuffa, Manuela Mancini, Gianluca Brusa, Eleonora Pagnotta, Claudia Maria Hattinger, Massimo Serra, Daniel Remondini, Gastone Castellani, Patrizia Corrado, Enza Barbieri, Maria Alessandra Santucci

Research output: Contribution to journalArticlepeer-review

Abstract

Purpose: To investigate the impact of TP53 (tumor protein 53, p53) on genomic stability of osteosarcoma (OS). Materials and 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.

Original languageEnglish
Pages (from-to)591-601
Number of pages11
JournalInternational Journal of Radiation Biology
Volume84
Issue number7
DOIs
Publication statusPublished - 2008

Keywords

  • Array-based comparative genomic hybridization
  • Mitochondrial DNA
  • Osteosarcoma
  • p53

ASJC Scopus subject areas

  • Agricultural and Biological Sciences (miscellaneous)
  • Radiology Nuclear Medicine and imaging
  • Radiological and Ultrasound Technology
  • Nuclear Energy and Engineering
  • Radiation

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