The Yield of DNA Double-strand Breaks Produced Intracellularly by Ionizing Radiation: A Review

Jf, Ward

doi:10.1080/09553009014551251

Cited by 290 publications

(142 citation statements)

References 25 publications

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“…Indeed, most of the in vivo and in vitro damage to biological systems from gamma radiation can be attributed to the hydroxyl (OH-) free radical [63,65,66]. These free radicals react with target collagen molecules within a lifetime on the order of 0.01-1 ns and render irrecoverable changes in the chemical structure of the collagen [62].…”

Section: Discussionmentioning

confidence: 99%

On the effect of X-ray irradiation on the deformation and fracture behavior of human cortical bone

Barth

Launey

MacDowell

et al. 2010

Bone

178

108

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In situ mechanical testing coupled with imaging using high-energy synchrotron x-ray diffraction or tomography imaging is gaining in popularity as a technique to investigate micrometer and even sub-micrometer deformation and fracture mechanisms in mineralized tissues, such as bone and teeth. However, the role of the irradiation in affecting the nature and properties of the tissue is not always taken into account. Accordingly, we examine here the effect of x-ray synchrotron-source irradiation on the mechanistic aspects of deformation and fracture in human cortical bone. Specifically, the strength, ductility and fracture resistance (both work-of-fracture and resistancecurve fracture toughness) of human femoral bone in the transverse (breaking) orientation were evaluated following exposures to 0.05, 70, 210 and 630 kGy irradiation. Our results show that the radiation typically used in tomography imaging can have a major and deleterious impact on the strength, post-yield behavior and fracture toughness of cortical bone, with the severity of the effect progressively increasing with higher doses of radiation. Plasticity was essentially suppressed after as little as 70 kGy of radiation; the fracture toughness was decreased by a factor of five after 210 kGy of radiation. Mechanistically, the irradiation was found to alter the salient toughening mechanisms, manifest by the progressive elimination of the bone's capacity for plastic deformation which restricts the intrinsic toughening from the formation "plastic zones" around crack-like defects. Deep-ultraviolet Raman spectroscopy indicated that this behavior could be related to degradation in the collagen integrity.

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Section: Discussionmentioning

confidence: 99%

On the effect of X-ray irradiation on the deformation and fracture behavior of human cortical bone

Barth

Launey

MacDowell

et al. 2010

Bone

178

108

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show abstract

“…Furthermore, the mechanisms that are proposed to vary the yield of radiation-induced DSBs formation are also expected to vary the yield of radiation-induced SSBs (Ward, 1990). Consequently, the extent of radiation-induced SSB formation can be considered a valid surrogate marker of radiogenic DSB formation.…”

mentioning

confidence: 99%

Measurements using the alkaline comet assay predict bladder cancer cell radiosensitivity

et al. 2003

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In the UK, the two main treatments of invasive bladder cancer are radiotherapy or cystectomy. However, B50% of patients undergoing radiotherapy fail to respond. If tumour radiosensitivity could be predicted in advance, it may be possible to improve control rates significantly by selecting for radiotherapy those patients whose tumours are radiosensitive. Additionally, patients who would benefit from surgery would be identified earlier. The alkaline comet assay (ACA) is a sensitive method for the detection of DNA strand break damage in cells. In the present study, using six bladder cancer cell lines of differing radiosensitivities, cell survival was compared to the manifestation of radiogenic DNA damage as assessed by ACA. For all the cell lines, the extent of comet formation strongly correlates with cell killing (R 2 40.96), with a greater response being noted in radiosensitive cells. In repair studies, measures of residual damage correlate with survival fraction at 2 Gy (R 2 40.96), but for only five of the cell lines. Finally, cells from human bladder tumour biopsies reveal a wide range of predicted radiosensitivies as determined by ACA. Overall, these studies demonstrate ACA to be a good predictive measure of bladder cancer cell radiosensitivity at low dose, with potential clinical application.

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“…In contrast, Ward (1990) argued that the yield of molecular lesions (initial damage) is independent of tumour cell type and that radiation-sensitive cells are repair deficient, resulting in different levels of residual damage. However, in our work, there were no significant differences in the slopes of the residual DNA dsb dose-response curves fitted by linear regression and SF2 after HDR and LDR irradiation.…”

Section: Discussionmentioning

confidence: 99%

The ratio of initial/residual DNA damage predicts intrinsic radiosensitivity in seven cervix carcinoma cell lines

Marples

Longhurst²,

Eastham³

et al. 1998

Br J Cancer

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Summary The single-cell gel electrophoresis (comet) assay was used to measure radiation-produced DNA double-strand breaks (dsbs) in a series of seven cervical tumour cell lines (ME180, HT3, C33A, C41, SiHa, MS751 and CaSki). The proportion of DNA dsbs was measured immediately after radiation treatment (initial damage) and 16 h later after incubation at 370C (residual damage). Linear dose-response curves were seen for initial (slopes 0.23-0.66) and residual (slopes 0.16-0.87) DNA dsbs. Neither of the slopes of the linear regression analysis on the initial and on the residual DNA dsbs dose-response curves (range 0-80 Gy) correlated with SF2 (surviving fraction at 2 Gy) measured after high-(HDR) or low-dose-rate (LDR) irradiation. An association was evident between SF2 after HDR and LDR irradiation and the ratio of the absolute level of initial and residual damage after a single dose of 60 Gy. However, a significant correlation was found between HDR (r= -0.78, P = 0.04) and LDR (r = -0.86, P = 0.03) SF2 values and the ratio of the slopes of the initial and residual DNA dsbs dose-response curves (range 0.47-0.99), representing the fraction of DNA damage remaining. These results indicate that the neutral comet assay can be used to predict radiosensitivity of cervical tumour cell lines by assessing the ratio of initial and residual DNA dsbs.

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The Yield of DNA Double-strand Breaks Produced Intracellularly by Ionizing Radiation: A Review

Cited by 290 publications

References 25 publications

On the effect of X-ray irradiation on the deformation and fracture behavior of human cortical bone

On the effect of X-ray irradiation on the deformation and fracture behavior of human cortical bone

Measurements using the alkaline comet assay predict bladder cancer cell radiosensitivity

The ratio of initial/residual DNA damage predicts intrinsic radiosensitivity in seven cervix carcinoma cell lines

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