Impaired DNA repair as assessed by the "comet" assay in patients with thyroid tumors after a history of radiation therapy: a preliminary study.
OBJECTIVE
Patients with a history of head and neck irradiation in childhood are at risk to develop thyroid tumors. The aim of this study was to determine if an impairement of DNA strand breaks repair could account for this observation.


METHODS
Circulating unstimulated lymphocytes of a group of 13 patients who developed thyroid tumors after radiotherapy were submitted to the alkaline single-cell gel electrophoresis assay (SCGE or "comet" assay) after in vitro exposure to 2 and 5 Gy of gamma-rays. A control group of 8 healthy donors and 2 cases with a history of neck irradiation who did not develop a thyroid tumor were also analysed. The immediate response was compared to that observed after 15, 30, and 60 min of postexposure incubation periods.


RESULTS
Induction of DNA strand breaks is a dose-dependent process. The SCGE assay parameters did not differ significantly between patients and controls immediately (t=0) after irradiation at the two doses used. As compared to healthy donors, a slower kinetics of repair was found in the patients. The proportion of residual damage at 60 min postirradiation was significantly (p < 0.01) higher in patients than in controls, at both doses analysed. Flow cytometric analysis of apoptosis and p53 protein status studied before and after irradiation showed no apparent relationship with the repair capacity.


CONCLUSIONS
This preliminary study suggests that a subgroup of patients who develop thyroid tumors after a history of irradiation are partially defective in the late restitution of in vitro radiation-induced DNA strand breaks. This deficiency could be a predisposing factor to radiation-associated thyroid tumorigenesis. Detection of susceptible individuals using the simple and rapid comet assay, especially children receiving radiotherapeutic treatment, may allow a preventive surveillance for radiation-associated epithelial thyroid tumor development.
Leprat
F
F
UMR 218 CNRS, Institut Curie, Recherche, LCR n 1 du CEA, Paris, France.
Alapetite
C
C
Rosselli
F
F
Ridet
A
A
Schlumberger
M
M
Sarasin
A
A
Suarez
H G
HG
Moustacchi
E
E
D000328:Adult; D017209:Apoptosis; D004247:DNA / Q000528:radiation effects; D004249:DNA Damage; D004260:DNA Repair; D004586:Electrophoresis / Q000379:methods; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009381:Neoplasms, Radiation-Induced / Q000235:genetics*; D013961:Thyroid Gland / Q000528:radiation effects; D013964:Thyroid Neoplasms / Q000235:genetics*
D004247:DNA