HNSCC cell lines positive for HPV and p16 possess higher cellular radiosensitivity due to an impaired DSB repair capacity.
Radiother Oncol
; 107(2): 242-6, 2013 May.
Article
em En
| MEDLINE
| ID: mdl-23602369
ABSTRACT
BACKGROUND AND PURPOSE:
When treated by radiotherapy, patients with squamous cell carcinomas of the head and neck (HNSCC) positive for HPV and p16(INK4a) possess a clearly favorable prognosis as compared to those with HPV-negative HNSCC. The aim of this work was to study whether the better outcomes might be caused by an enhanced cellular radiosensitivity. MATERIALS ANDMETHODS:
The radiation response of five HPV/p16(INK4a)-positive and five HPV-negative cell lines was characterized with regard to cellular radiosensitivity by colony formation assay. Furthermore G1- and G2-arrest, apoptosis and residual DNA double-strand breaks (DSB) were analyzed by the colcemid-based G1-efflux assay, propidium iodide staining, the detection of PARP cleavage, the fluorescence-based detection of caspase activity and the immunofluorescence staining of γH2AX and 53BP1 foci.RESULTS:
On average, the cellular radiosensitivity of the HNSCC cell lines positive for HPV and p16(INK4a) was higher as compared to the sensitivity of a panel of five HPV-negative HNSCC cell lines (SF3=0.2827 vs. 0.4455). The higher sensitivity does not result from increased apoptosis or the execution of a permanent G1-arrest, but is rather associated with both, elevated levels of residual DSBs and extensive G2-arrest.CONCLUSIONS:
Increased cellular radiosensitivity due to compromised DNA repair capacity is likely to contribute to the improved outcome of patients with HPV/p16(INK4a)-positive tumors when treated by radiotherapy.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Papillomaviridae
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Tolerância a Radiação
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Carcinoma de Células Escamosas
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Reparo do DNA
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Quebras de DNA de Cadeia Dupla
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Neoplasias de Cabeça e Pescoço
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Proteínas de Neoplasias
Limite:
Humans
Idioma:
En
Revista:
Radiother Oncol
Ano de publicação:
2013
Tipo de documento:
Article
País de afiliação:
Alemanha