IMPAIRED DNA-REPAIR AS ASSESSED BY THE COMET ASSAY IN PATIENTS WITH THYROID-TUMORS AFTER A HISTORY OF RADIATION-THERAPY - A PRELIMINARY-STUDY

Purpose: Patients with a history of head and neck irradiation in child hood are at risk to develop thyroid tumors. The aim of this study was to determine if an impairement of DNA strand breaks repair could accou nt for this observation.Methods and Materials: Circulating unstimulate d lymphocytes of a group of 13 patients who developed thyroid tumors a fter radiotherapy were submitted to the alkaline single-cell gel elect rophoresis 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 ca ses with a history of neck irradiation who did not develop a thyroid t umor were also analysed. The immediate response was compared to that o bserved after 15, 30, and 60 min of postexposure incubation periods. R esults: Induction of DNA strand breaks is a dose-dependent process. Th e SCGE assay parameters did not differ significantly between patients and controls immediately (t = 0) after irradiation at the two doses us ed. As compared to healthy donors, a slower kinetics of repair was fou nd in the patients. The proportion of residual damage at 60 min postir radiation was significantly (p < 0.01) higher in patients than in cont rols, at both doses analysed. Flow cytometric analysis of apoptosis an d p53 protein status studied before and after irradiation showed no ap parent relationship with the repair capacity. Conclusion: This prelimi nary study suggests that a subgroup of patients who develop thyroid tu mors after a history of irradiation are partially defective in the lat e restitution of in vitro radiation-induced DNA strand breaks. This de ficiency could be a predisposing factor to radiation-associated thyroi d tumorigenesis. Detection of susceptible individuals using the simple and rapid comet assay, especially children receiving radiotherapeutic treatment, may allow a preventive surveillance for radiation-associat ed epithelial thyroid tumor development. (C) 1998 Elsevier Science Inc .