P53 oncosuppressor influences selection of genomic imbalances in response to ionizing radiations in human osteosarcoma cell line SAOS-2.
Int J Radiat Biol
; 84(7): 591-601, 2008 Jul.
Article
em En
| MEDLINE
| ID: mdl-18661375
ABSTRACT
PURPOSE:
To investigate the impact of TP53 (tumor protein 53, p53) on genomic stability of osteosarcoma (OS). MATERIALS ANDMETHODS:
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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Osteoblastos
/
Radiação Ionizante
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DNA Mitocondrial
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Osteossarcoma
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Proteína Supressora de Tumor p53
/
Espécies Reativas de Oxigênio
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Instabilidade Genômica
Limite:
Humans
Idioma:
En
Ano de publicação:
2008
Tipo de documento:
Article