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 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 and Materials: Circulating unstimulated lymphocytes of a...

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Veröffentlicht in:International journal of radiation oncology, biology, physics biology, physics, 1998-03, Vol.40 (5), p.1019-1026
Hauptverfasser: Leprat, Frederic, Alapetite, Claire, Rosselli, Filippo, Ridet, Agnès, Schlumberger, Martin, Sarasin, Alain, Suarez, Horacio G., Moustacchi, Ethel
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container_end_page 1026
container_issue 5
container_start_page 1019
container_title International journal of radiation oncology, biology, physics
container_volume 40
creator Leprat, Frederic
Alapetite, Claire
Rosselli, Filippo
Ridet, Agnès
Schlumberger, Martin
Sarasin, Alain
Suarez, Horacio G.
Moustacchi, Ethel
description Purpose: 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 and Materials: 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 γ-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. Conclusion: 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.
doi_str_mv 10.1016/S0360-3016(97)00914-0
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The aim of this study was to determine if an impairement of DNA strand breaks repair could account for this observation. Methods and Materials: 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 γ-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 &lt; 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. Conclusion: 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. 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The aim of this study was to determine if an impairement of DNA strand breaks repair could account for this observation. Methods and Materials: 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 γ-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 &lt; 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. Conclusion: 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. 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The aim of this study was to determine if an impairement of DNA strand breaks repair could account for this observation. Methods and Materials: 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 γ-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 &lt; 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. Conclusion: 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.</abstract><cop>New York, NY</cop><pub>Elsevier Inc</pub><pmid>9539555</pmid><doi>10.1016/S0360-3016(97)00914-0</doi><tpages>8</tpages></addata></record>
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identifier ISSN: 0360-3016
ispartof International journal of radiation oncology, biology, physics, 1998-03, Vol.40 (5), p.1019-1026
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1879-355X
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source MEDLINE; Elsevier ScienceDirect Journals
subjects Adult
Apoptosis
Biological and medical sciences
Blood leukocytes
Carcinogenesis, carcinogens and anticarcinogens
DNA - radiation effects
DNA Damage
DNA Repair
Electrophoresis - methods
Endocrinopathies
Female
Humans
Male
Malignant tumors
Medical sciences
Middle Aged
Neoplasms, Radiation-Induced - genetics
Physical agents
Radiation-induced
Single cell gel electrophoresis assay
Thyroid cancer
Thyroid Gland - radiation effects
Thyroid Neoplasms - genetics
Thyroid. Thyroid axis (diseases)
Tumors
title Impaired DNA Repair as Assessed by the “Comet” Assay in Patients with Thyroid Tumors After a History of Radiation Therapy: A Preliminary Study
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