Radiation sensitivity, H2AX phosphorylation, and kinetics of repair of DNA strand breaks in irradiated cervical cancer cell lines.
Cancer Res
; 64(19): 7144-9, 2004 Oct 01.
Article
em En
| MEDLINE
| ID: mdl-15466212
ABSTRACT
Six human cervical cancer cell lines [five human papillomavirus (HPV) positive, one HPV negative] for induction and rejoining of DNA strand breaks and for kinetics of formation and loss of serine 139 phosphorylated histone H2AX (gammaH2AX). X-rays induced the same level of DNA breakage for all cell lines. By 8 hours after 20 Gy, <2% of the initial single-strand breaks remained and no double-strand breaks could be detected. In contrast, 24 hours after irradiation, gammaH2AX representing up to 30% of the initial signal still present. SW756 cells showed almost four times higher background levels of gammaH2AX and no residual gammaH2AX compared with the most radiosensitive HPV-negative C33A cells that showed the lowest background and retained 30% of the maximum level of gammaH2AX. Radiation sensitivity, measured as clonogenic-surviving fraction after 2 Gy, was correlated with the fraction of gammaH2AX remaining 24 hours after irradiation. A substantial correlation with gammaH2AX loss half-time measured over the first 4 hours was seen only when cervical cell lines were included in a larger series of p53-deficient cell lines. Interestingly, p53 wild-type cell lines consistently showed faster gammaH2AX loss half-times than p53-deficient cell lines. We conclude that cell line-dependent differences in loss of gammaH2AX after irradiation are related in part to intrinsic radiosensitivity. The possibility that the presence of gammaH2AX foci may not always signify the presence of a physical break, notably in some tumor cell lines, is also supported by these results.
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Base de dados:
MEDLINE
Assunto principal:
Tolerância a Radiação
/
Dano ao DNA
/
DNA de Neoplasias
/
Histonas
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Neoplasias do Colo do Útero
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Reparo do DNA
Idioma:
En
Ano de publicação:
2004
Tipo de documento:
Article