Clustered double-strand breaks in heterochromatin perturb DNA repair after high linear energy transfer irradiation.
Radiother Oncol
; 121(1): 154-161, 2016 10.
Article
em En
| MEDLINE
| ID: mdl-27637859
ABSTRACT
BACKGROUND AND PURPOSE:
High linear energy transfer (LET) radiotherapy offers superior dose conformity and biological effectiveness compared with low-LET radiotherapy, representing a promising alternative for radioresistant tumours. A prevailing hypothesis is that energy deposition along the high-LET particle trajectories induces DNA lesions that are more complex and clustered and therefore more challenging to repair. The precise molecular mechanisms underlying the differences in radiobiological effects between high-LET and low-LET radiotherapies remain unclear. MATERIAL ANDMETHODS:
Human fibroblasts were irradiated with high-LET carbon ions or low-LET photons. At 0.5h and 5h post exposure, the DNA-damage pattern in the chromatin ultrastructure was visualised using gold-labelled DNA-repair factors. The induction and repair of single-strand breaks, double-strand breaks (DSBs), and clustered lesions were analysed in combination with terminal dUTP nick-end labelling of DNA breaks.RESULTS:
High-LET irradiation induced clustered lesions with multiple DSBs along ion trajectories predominantly in heterochromatic regions. The cluster size increased over time, suggesting inefficient DSB repair. Low-LET irradiation induced many isolated DSBs throughout the nucleus, most of which were efficiently rejoined.CONCLUSIONS:
The clustering of DSBs in heterochromatin following high-LET irradiation perturbs efficient DNA repair, leading to greater biological effectiveness of high-LET irradiation versus that of low-LET irradiation.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
DNA
/
Heterocromatina
/
Reparo do DNA
/
Quebras de DNA de Cadeia Dupla
/
Fibroblastos
Limite:
Humans
Idioma:
En
Revista:
Radiother Oncol
Ano de publicação:
2016
Tipo de documento:
Article
País de afiliação:
Alemanha