Relationship between cellular radiosensitivity and DNA damage measured by comet assay in human normal, NBS and AT fibroblasts

Brammer, I.; Zöller, Margot; Dikomey, Ekkehard

doi:10.1080/09553000110064222

Cited by 34 publications

(15 citation statements)

References 42 publications

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“…Similarly, genetic variants in base excision repair genes can affect the amount of DNA damage induced by irradiation (33). It was suggested that the variability detected with the comet technique in the initial damage of cells with different genetic background might point at a difference in the DNA attachment in the nuclear matrix or in chromatin density (21). In most of the clinical studies cited previously, the initial DNA damage was shown to correlate with radiation sensitivity, mainly when late effects of a therapy were evaluated.…”

Section: Discussionmentioning

confidence: 98%

“…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 9…”

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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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Section: Discussionmentioning

confidence: 98%

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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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“…Therefore, differences in the induction of DNA damage are related to both differences in the chromatin structure and differences in the cellular radiosensitivity. In the comet assay, the size of the comet tail depends not only on the number of DNA damage but also on differences in the chromatin structure under both the neutral and alkaline conditions [6,10,12]. It is therefore considered that we could detect the differences in the initial DNA damage that were related to cellular radiosensitivity among the three cell lines.…”

Section: Discussionmentioning

confidence: 88%

The Relationship between Cellular Radiosensitivity and Radiation-Induced DNA Damage Measured by the Comet Assay

Wada

Kurahayashi

Kobayashi

et al. 2003

The Journal of Veterinary Medical Science

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ABSTRACT. The relationship between deoxyribonucleic acid (DNA) damage and the cell death induced by γ-irradiation was examined in three kinds of cells, Chinese hamster ovary fibroblast CHO-K1, human melanoma HMV-II and mouse leukemia L5178Y. Cell survival was determined by a clonogenic assay. The induction and rejoining of DNA strand breaks induced by radiation were measured by the alkaline and neutral comet assays. L5178Y cells were the most radiosensitive, while CHO-K1 cells and HMV-II cells were radioresistant. There was an inverse relationship between the survival fraction at 2 Gy (SF2) and the yield of initial DNA strand breaks per unit dose under the alkaline condition for the comet assay, and also a relationship between SF2 and the residual DNA strand breaks (for 4 hr after irradiation) under the neutral condition for the comet assay, the latter being generally considered to be relative to cellular radiosensitivity. In the present analysis, it was considered that the alkaline condition for the comet assay was optimal for evaluating the initial DNA strand breaks, while the neutral condition was optimal for evaluating the residual DNA strand breaks. Since the comet assay is simpler and more rapid than other methods for detecting radiation-induced DNA damage, this assay appears to be a useful predictive assay for evaluating cellular clonogenic radiosensitivity of tumor cells. KEY WORDS: comet assay, DNA strand break, γ-irradiation, predictive assay, radiosensitivity.J. Vet. Med. Sci. 65(4): 471-477, 2003 Different types of cell lines show different radiosensitivities. In addition, even a tumor of the same origin and pathology, can show radiosensitivity over quite a wide range [4], and therefore, understanding the radiosensitivity of an individual tumor is of great importance in the clinical situation. Knowledge of the intrinsic radiosensitivities of cells from a tumor biopsy can help produce an optimized radiotherapy protocol for individual patients.Reproductive death measured by a clonogenic assay is an important index for the cell death induced by radiation, and the cellular radiosensitivities of fibroblasts and tumor cells have been evaluated by a clonogenic assay [13,17]. A good correlation was found between the reproductive death of fibroblasts measured by the clonogenic assay and the severity of late normal tissue effects, such as fibrosis and erythema, after radiotherapy [7,14]. However, this clonogenic assay consumes a lot of time, and the cells must be proliferated in vitro [4,14]. Hence this assay is not optimal for routine clinical use, and thus there is now much interest in exploiting a more rapid and simple assay to evaluate cellular radiosensitivity [8,25].It is said that the cell death caused by radiation is due to deoxyribonucleic acid (DNA) damage [29]. DNA double strand breaks (dsbs) are considered to be closely related to cell death because it is suggested that they can lead directly to chromosome aberration and the loss of genetic material [22]. To date, the correlation between radiose...

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“…A correlation between cellular radiosensitivity and initial DNA damage with retention of chromatin structure has recently been reported [3], while other studies have suggested the lack of such a correlation [6,21]. Chromatin structure stability may be an important factor that relates not only to intercellular differences in initial DNA damage, but also to radiosensitivity [14,15].…”

Section: Discussionmentioning

confidence: 99%

Prediction of Cellular Radiosensitivity from DNA Damage Induced by .GAMMA.-Rays and Carbon Ion Irradiation in Canine Tumor Cells

Wada¹,

Khoa²,

Kobayashi³

et al. 2005

The Journal of Veterinary Medical Science

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ABSTRACT. Diseases of companion animals are shifting from infectious diseases to neoplasms (cancer), and since radiation therapy is one of the effective choices available for cancer treatment, the application of radiotherapy in veterinary medicine is likely to increase. However tumor tissues have different radiosensitivities, and therefore it is important to determine the intrinsic radiosensitivity of tumors in individual patients in advance of radiotherapy. We have studied the relationship between the surviving cell fraction measured by a clonogenic assay and DNA double strand breaks detected by a comet assay under neutral conditions in three canine tumor cell lines, after γ-ray and carbon ion irradiation. In all the cell lines, cell death assessed by the clonogenic assay was much higher following irradiation with carbon ions than with γ-rays. The initial and residual (4 hr) DNA damage due to γ-ray and carbon ion irradiation were higher in a radiosensitive cell line than in a radioresistant cell line. The surviving cell fraction at 2 Gy (SF2) showed a tendency for correlation with both the initial and residual DNA damage. In particular, the residual damage per Gy was significantly correlated with SF2, regardless of the type of radiation. This indicates that cellular radiosensitivity can be predicted by detection of radiation-induced residual DNA damage. KEY WORDS: canine tumor cell, comet assay, DNA damage, radiosensitivity, radiotherapy.J. Vet. Med. Sci. 67(11): 1089-1095, 2005 Due to recent improvements in the breeding environment and veterinary preventive medicine, companion animals live much longer than in the past. These improvements have made it possible to reduce severe infectious diseases, but conversely the incidence of tumors is increasing in animals. Radiation therapy is one of the effective choices available against such tumors and its use in veterinary medicine is likely to increase.In human medicine, advances have been made in new technologies, such as low linear energy transfer (LET) radiation using protons [16] and linear accelerator (LINAC) three dimensional X-rays. Because high LET radiation causes higher reproductive cell death than proton irradiation [5], clinical studies of radiation therapy using heavy-ion beams have started. However, a wide range of radiosensitivity is observed, even for tumors of the same histopathological origin [2]. Therefore, to improve local control of the tumor, and to set up an effective treatment plan with minimal side effects, it is necessary to predict the radiosensitivity of the tumor for an individual patient, both for high and low LET radiation. Therefore, development of a predictive assay for tumor radiosensitivity in medical practice and establishment of biological parameters are of importance.In general, the clonogenic survival assay is regarded as a good measure of radiosensitivity related to the effects of radiotherapy [4]. A good correlation has been found between the reproductive death of fibroblasts measured by the clonogenic assay and the severity of...

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Relationship between cellular radiosensitivity and DNA damage measured by comet assay in human normal, NBS and AT fibroblasts

Abstract: The correlation between SF2 and the initial tail moment at 5 Gy found here suggests that the cellular radiosensitivity of human fibroblasts also depends on the chromatin structure.

Cited by 34 publications

References 42 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

The Relationship between Cellular Radiosensitivity and Radiation-Induced DNA Damage Measured by the Comet Assay

Prediction of Cellular Radiosensitivity from DNA Damage Induced by .GAMMA.-Rays and Carbon Ion Irradiation in Canine Tumor Cells

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