Impaired DNA Repair as Assessed by the “Comet” Assay in Patients with Thyroid Tumors After a History of Radiation Therapy: A Preliminary Study

Leprat, F.; Alapetite, Claire; Rosselli, Filippo; Ridet, Agnès; Schlumberger, Martin; Sarasin, Alain; Suárez, H. G.; Moustacchi, E.

doi:10.1016/s0360-3016(97)00914-0

Cited by 52 publications

(20 citation statements)

References 21 publications

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“…Using the comet assay, enhanced initial damage and reduced repair capacity in vitro were characterized for ataxia telangiectasia patients (20,21). Furthermore, significant differences in DNA repair kinetics were detected between patients with severe skin reactions and patients with normal reactions to radiation when the alkaline R E T R A C T E D , A p r i l 2 1 , 2 0 0 9Imaging, Diagnosis, Prognosis comet assay was used (13,22). However, these studies suffer from several weaknesses, among them the retrospective casecontrol study design with unclear selection of participants and insufficient characterization of therapy modalities and side effect documentation (23).…”

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confidence: 99%

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Correlation between DNA Repair Capacity in Lymphocytes and Acute Side Effects to Skin during Radiotherapy in Nasopharyngeal Cancer Patients

Wang

Chen²,

Li³

et al. 2005

Clinical Cancer Research

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Purpose: Repair of radiation-induced DNA damage plays a critical role for both the susceptibility of patients to side effects after radiotherapy and their subsequent cancer risk.The study objective was to evaluate whether DNA repair data determined in vitro are correlated with the occurrence of acute side effects during radiotherapy. Experimental Design: Nasopharyngeal cancer patients receiving radiation therapy were recruited in a prospective epidemiologic study. As an indicator for clinical radiosensitivity, adverse reactions of the skin were recorded. Cryopreserved lymphocytes from 100 study participants were g-irradiated with 5 Gy in vitro and analyzed using the alkaline comet assay. Reproducibility of the assay was determined by repeated analysis (n = 22) of cells from a healthy donor. A coefficient of variation of 0.24 was calculated. Results: The various parameters determined to characterize the individual DNA repair capacity showed large differences between patients. Twenty-one patients were identified with considerably enhanced DNA damage induction, and 19 patients exhibited severely reduced DNA repair capacity after 15 and 30 minutes. Eight patients were considered as clinically radiosensitive, indicated by moist desquamation of the skin after a total radiation dose of 70 Gy. Conclusions: Using the alkaline comet assay as described here, nasopharyngeal cancer patients were identified showing abnormal cellular radiation effects, but this repair deficiency corresponded only at a very limited extent to the acute radiation sensitivity of the skin.Despite various therapeutic improvements, efficient radiation therapy of malignant cancers is limited by the adverse side effects occurring in the normal tissue when exposed to radiation. In general, >15% of nasopharyngeal cancer patients develop acute or late symptoms of enhanced radiosensitivity (1, 2). Several patient-and treatment-related factors are known to influence the variability of side effects; however, up to 70% of the cases remain unexplained (1). Therefore, there is much interest among clinicians for in vitro detection of cellular radiosensitivity as an indicator of the extent of a patient's normal tissue reaction (3). The use of such predictive assays would enable clinicians to adjust radiation therapy for both sensitive and resistant patients (4) with consequent improvement in the therapeutic ratio (5). For example, a strategy based on testing human normal tissue radiosensitivity to identify the patients with a high risk of developing unacceptable severe reactions after radiotherapy might also permit the individualization of treatment (5) by dose escalation in resistant patients without increasing normal tissue complications (6 -8).Three biological parameters have been used mainly to determine radiosensitivity in vitro. Data from assays based on clonogenic survival (9 -12) and chromosomal aberrations (11,12) showed, at least in several studies, a good correlation of in vitro data with late radiation effects, but these assays are time consu...

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confidence: 99%

“…Imaging, Diagnosis, Prognosis comet assay was used (13,22). However, these studies suffer from several weaknesses, among them the retrospective casecontrol study design with unclear selection of participants and insufficient characterization of therapy modalities and side effect documentation (23).…”

mentioning

confidence: 99%

Correlation between DNA Repair Capacity in Lymphocytes and Acute Side Effects to Skin during Radiotherapy in Nasopharyngeal Cancer Patients

Wang

Chen²,

Li³

et al. 2005

Clinical Cancer Research

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“…The higher repair half-time values in the FA groups may simply reflect their excess initial TM over the initial TM of the controls rather than a slower DNA repair. In this context it should be noted that increased levels of residual DNA damage were previously reported for irradiated peripheral blood lymphocytes of breast cancer over-reactors (Alapetite et al, 1999) and patients with thyroid tumors (Leprat et al, 1998).…”

Section: Discussionmentioning

confidence: 71%

Response to X-Irradiation of Fanconi Anemia Homozygous and Heterozygous Cells Assessed by the Single-Cell Gel Electrophoresis (Comet) Assay

Djuzenova

Rothfuß

Oppitz

et al. 2001

Laboratory Investigation

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SUMMARY:Fanconi anemia (FA) is an autosomal recessive disorder characterized by bone marrow failure and cancer susceptibility. Patient cells are sensitive to a variety of clastogens, most prominently cross-linking agents. Although there is the long-standing clinical impression of radiosensitivity, in vitro studies have yielded conflicting results. We exposed peripheral blood mononuclear cells from FA patients and carriers to x-rays and determined their DNA damage and repair profiles using the alkaline single-cell gel electrophoresis (comet) assay. Studies were carried out in two independent series of experiments by two laboratories using different protocols. The cells of both FA patients and carriers showed uniformly high initial DNA damage rates as assessed by the total initial tail moment. In addition, the average residual tail moment at 30 to 50 minutes and the repair half-time parameters were significantly elevated. These findings suggest an increased release of fragmented DNA following x-ray exposure in cells that carry one or two mutations in one of the FA genes. The comet assay may be a useful adjunct for heterozygote detection in families of FA patients. (Lab Invest 2001, 81:185-192).

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“…The CA method has also been applied in several small pilot studies, comparing the DNA repair capacity between cancer patients and healthy subjects (Alapetite et al, 1999;Leprat et al, 1998;Djuzenova, et al, 2006;Zhang et al, 2006). In these studies, the CA has demonstrated an impaired DNA lesion repair capacity in the lymphocytes of cancer www.intechopen.com patients, when compared to that of the healthy controls.…”

Section: Discussionmentioning

confidence: 99%

The Biliprotein C-Phycocyanin Modulates the DNA Damage Response in Lymphocytes from Nuclear Power Plant Workers

Stankova¹,

Ivanova²,

Nikolov³

et al. 2011

Nuclear Power - Operation, Safety and Environment

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Impaired DNA Repair as Assessed by the “Comet” Assay in Patients with Thyroid Tumors After a History of Radiation Therapy: A Preliminary Study

Cited by 52 publications

References 21 publications

Correlation between DNA Repair Capacity in Lymphocytes and Acute Side Effects to Skin during Radiotherapy in Nasopharyngeal Cancer Patients

Correlation between DNA Repair Capacity in Lymphocytes and Acute Side Effects to Skin during Radiotherapy in Nasopharyngeal Cancer Patients

Response to X-Irradiation of Fanconi Anemia Homozygous and Heterozygous Cells Assessed by the Single-Cell Gel Electrophoresis (Comet) Assay

The Biliprotein C-Phycocyanin Modulates the DNA Damage Response in Lymphocytes from Nuclear Power Plant Workers

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