DNA Organization Affects Cellular Radiosensitivity and Detection of Initial DNA Strand Breaks

Olive, Peggy L.

doi:10.1080/09553009214552261

Cited by 63 publications

(21 citation statements)

References 59 publications

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“…Nonirradiated cells very rarely showed a tail and a signal on it, whereas cells irradiated with 3 Gy always presented a tail, which could vary in size and could contain several signals. This was confirmed by the measure of tail moment (% DNA Â tail length), which is directly proportional to DNA damage and indeed is found to be much higher in irradiated cells (39,40). The analysis of DNA damage in the two cell lines, before and after irradiation, showed also that the tail moment was in general more elevated in lymphoblastoid cells (Table 1).…”

Section: Resultssupporting

confidence: 56%

Enhanced Sensitivity of the RET Proto-Oncogene to Ionizing Radiation In vitro

Volpato

Martínez-Alfaro²,

Corvi³

et al. 2008

Cancer Research

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Exposure to ionizing radiation is a well-known risk factor for a number of human cancers, including leukemia and thyroid cancer. It has been known for a long time that exposure of cells to radiation results in extensive DNA damage; however, a small number of studies have tried to explain the mechanisms of radiation-induced carcinogenesis. The high prevalence of RET/PTC rearrangements in patients who have received external radiation, and the evidence of in vitro induction of RET rearrangements in human cells, suggest an enhanced sensitivity of the RET genomic region to damage by ionizing radiation. To assess whether RET is indeed more sensitive to radiations than other genomic regions, we used a COMET assay coupled with fluorescence in situ hybridization, which allows the measurement of DNA fragmentation in defined genomic regions of single cells. We compared the initial DNA damage of the genomic regions of RET, CXCL12/SDF1, ABL, MYC, PLA2G2A, p53, and JAK2 induced by ionizing radiation in both a lymphoblastoid and a fetal thyroid cell line. In both cell lines, RET fragmentation was significantly higher than in other genomic regions. Moreover, a differential distribution of signals within the COMET was associated with a higher percentage of RET fragments in the tail. RET was more susceptible to fragmentation in the thyroid-derived cells than in lymphoblasts. This enhanced susceptibility of RET to ionizing radiation suggests the possibility of using it as a radiation exposure marker. [Cancer Res 2008;68(21):8986-92]

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Section: Resultssupporting

confidence: 56%

Enhanced Sensitivity of the RET Proto-Oncogene to Ionizing Radiation In vitro

Volpato

Martínez-Alfaro²,

Corvi³

et al. 2008

Cancer Research

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“…Explanations of these variations in conclusion may lie either in technical aspects of the assays used or in the cell types being analysed. It has been suggested that in some assays apparent differences in strand breaks may be a result of differences in features of the cells other than their sensitivity to damage induction (Schwartz & Vaughan, 1989;Olive, 1992). It is, however, clear that differences would not be expected to explain sensitivity in every cell system, as it is clear that cells with repair differences do exist and these would not be expected to show differences in damage induction.…”

mentioning

confidence: 90%

Initial radiation-induced DNA damage in human tumour cell lines: a correlation with intrinsic cellular radiosensitivity

Almodóvar

Núñez²,

McMillan³

et al. 1994

Br J Cancer

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Summary The role of the initial DNA double-strand breaks (dsb) as a determinant of cellular radiosensitivity was studied in human breast and bladder cancer cell lines. Cell survival was measured by monolayer colony-forming assay as appropriate and differences in radiosensitivity were seen (a-values ranged from 0.12 to 0.54). After pulsed-field gel electrophoresis (PFGE) the initial slopes of dose-response curves were biphasic with a flattening of the curves above 30 Gy. When the frequency of DNA dsb induction was assessed using a mathematical model based on the DNA fragment size distribution into the gel lane, we found a statistically significant relationship between the number of DNA dsb induced and the corresponding a-values and fraction surviving after 2Gy (P = 0.0049 and P = 0.0031 respectively). These results support the view that initial damage is a major determinant of cell radiosensitivity.

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“…We interpreted our results to suggest that the differences between resistant and sensitive lines in elution rates after low-dose exposures most likely reflect alterations in chromosome structure (Schwartz et al, 1991;Olive, 1992;Schwartz and Vaughan, 1993), and thus it is likely that both initial break frequency and rejoining rate reflect alterations in chromosome structure. Differences in how DNA doublestrand break frequencies are measured in each laboratory may account for the slightly different results and conclusions concerning which parameter best correlates with clonogenic survival.…”

Section: Discussionmentioning

confidence: 97%

“…X-radiation sensitivity was determined by clonogenic survival assay (Weichselbaum et al, 1988a(Weichselbaum et al, , 1989 (Schwartz et al, 1990) Cells were exposed to 100 Gy of 6'Co gamma rays. While elution rates can be measured after exposures to lower doses, interexperimental variability is usually greater at low doses and elution rates may be influenced more by chromosome structure (Schwartz et al, 1991;Olive, 1992;Schwartz and Vaughan, 1993 We examined DNA double-strand break frequencies after a 1 h incubation in complete medium at 20°C. We chose this time point because in our original studies (Schwartz et al, 1988), the 1 h time point gave us the biggest differences between resistant and sensitive cells.…”

mentioning

confidence: 99%

DNA double-strand break rejoining rates, inherent radiation sensitivity and human tumour response to radiotherapy

Schwartz

Mustafi²,

Beckett³

et al. 1996

Br J Cancer

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SummaryThe relationship between DNA double-strand break rejoining rates, inherent radiation sensitivity and tumour response to radiation therapy was determined for a group of 25 squamous cell carcinoma (SCC) and eight sarcoma (SAR) tumours. DNA double-strand break frequencies were measured by neutral filter elution in first passage following explant tumour samples after in vitro exposure to 100 Gy of 6OCo gammarays. There was no significant difference between SCC and SAR tumour cells in their sensitivity to break induction, but in a 1 h time period SAR tumour cells rejoined significantly fewer breaks than SCC tumour cells, consistent with the greater sensitivity of SAR and suggesting that differences in rates of break rejoining account for the different distributions of radiosensitivities seen when different tumour types are compared. The percentage of breaks rejoined in 1 h in these tumour samples correlated well with Do and with the ,B component of the survival curve, measured in vitro by clonogenic assay in tumour cell lines established from the tumour samples, but not with SF2 or the a component of the survival curve. The rates of DNA double-strand break rejoining therefore appear to influence the exponential portion of survival curves and probably the interactions between breaks. The percentage of breaks rejoined in 1 h was higher in SCC tumours that subsequently failed radiotherapy and, although the differences were not significant, they suggest that rates of break rejoining are an important component of tumour response to radiation therapy.Keywords: predictive assay; DNA double-strand break repair; squamous cell carcinoma; sarcomaThe inherent sensitivity of cells within a tumour is thought to be an important component of radiation response. Both Fertil and Malaise (1985) and Deacon et al. (1984) reported large variations in the initial portions of in vitro survival curves from tumour cells of various histological types that they suggested might be related to radiotherapy response in vivo. Tumour types that are more difficult to control by radiotherapy produced cell lines that were more resistant to radiation in vitro. Weichselbaum et al. (1988a) reported that head and neck squamous cell carcinoma (SCC) tumour cells from radiotherapy failures were more resistant to radiation, as measured by in vitro survival curve analysis, than tumour cells derived from SCC pretreatment samples. Several investigators have examined the predictive value of in vitro survival curve measurements, principally SF2, the survival level after a 2 Gy exposure, with varying success (Brock et al., 1990;West et al., 1992West and Hendry, 1993;Girinsky et al., 1992 were faster in the more radioresistant cell lines (Schwartz et al., 1988). We subsequently confirmed this observation measuring DNA double-strand break rejoining with pulsedfield gel electrophoresis (Giaccia et al., 1992) and showed that chromosome break rejoining kinetics were also faster in the more resistant cells (Schwartz and Vaughan, 1989). Our studies suggest that the...

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DNA Organization Affects Cellular Radiosensitivity and Detection of Initial DNA Strand Breaks

Cited by 63 publications

References 59 publications

Enhanced Sensitivity of the RET Proto-Oncogene to Ionizing Radiation In vitro

Enhanced Sensitivity of the RET Proto-Oncogene to Ionizing Radiation In vitro

Initial radiation-induced DNA damage in human tumour cell lines: a correlation with intrinsic cellular radiosensitivity

DNA double-strand break rejoining rates, inherent radiation sensitivity and human tumour response to radiotherapy

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