DNA Damage Produced by Ionizing Radiation in Mammalian Cells: Identities, Mechanisms of Formation, and Reparability

Jf, Ward

doi:10.1016/s0079-6603(08)60611-x

Cited by 1,311 publications

(757 citation statements)

References 58 publications

Supporting

Mentioning

730

Contrasting

Unclassified

Order By: Relevance

“…The rationale for these investigations has been the general agreement that DSBs are the most critical of DNA-damaging lesions (Ward, 1988). However, the studies have shown little agreement as to whether initial DSBs vary between cell types.…”

Section: Discussionmentioning

confidence: 99%

Potential use of the alkaline comet assay as a predictor of bladder tumour response to radiation

et al. 2003

View full text Add to dashboard Cite

Bladder tumours show a variable response to radiotherapy with only about 50% showing good local control; currently there is no test to predict outcome prior to treatment. We have used five bladder tumour cell lines (T24, UM-UC-3, TCC-SUP, RT112, HT1376) to investigate the potential of the alkaline comet assay (ACA) to predict radiosensitivity. Radiation-induced DNA damage and repair were compared to clonogenic survival. When the five cell lines were irradiated and initial DNA damage was plotted against cell survival, at all doses (0 -6 Gy), a significant correlation was found (r 2 ¼ 0.9514). Following 4 Gy X-irradiation, all cell lines, except T24, showed a correlation between SF2 vs half-time for repair and SF2 vs residual damage at 5, 10, 20 and 30 min. The T24 cell line showed radioresistance at low doses (0 -2 Gy) and radiosensitivity at higher doses (4 -6 Gy) using both cell survival and ACA end points, explaining the lack of correlation observed for this cell line. These data indicate that initial DNA damage and residual damage can be used to predict for radiosensitivity. Our data suggest that predictive tests of radiosensitivity, appropriate to the clinical situation, may require the use of test doses in the clinical range.

show abstract

Section: Discussionmentioning

confidence: 99%

Potential use of the alkaline comet assay as a predictor of bladder tumour response to radiation

et al. 2003

View full text Add to dashboard Cite

show abstract

“…DNA is the most important cellular target for the lethal effects of ionising radiation, with double-strand breaks (DSBs) proposed to be the principal lesions responsible for radiogenic cell killing (Ward, 1988;Iliakis, 1991). Unfortunately, the relative yield of radiogenic DSBs is low, and high radiation doses tend to be required to produce measurable levels; doses that are far greater than those used clinically.…”

mentioning

confidence: 99%

“…In contrast with DSBs, the yield of radiation-induced singlestrand breaks (SSBs) is far greater (Ward, 1988), and can be readily measured at low clinically relevant doses of radiation. 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).…”

mentioning

confidence: 99%

Measurements using the alkaline comet assay predict bladder cancer cell radiosensitivity

et al. 2003

View full text Add to dashboard Cite

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.

show abstract

“…It is generally accepted that among the DNA damage induced mainly double-strand breaks (dsb) (Bryant, 1984;Ward, 1988;Wurm et al, 1994;Dikomey et al, 1998;Pfeiffer et al, 2000), and particularly residual dsb (Dikomey et al, 1998(Dikomey et al, , 2000 are responsible for cell killing by ionising radiation. The number of residual dsb depends on both, the number of dsb induced and on the respective repair capacity.…”

mentioning

confidence: 99%

Radiosensitivity of human tumour cells is correlated with the induction but not with the repair of DNA double-strand breaks

2003

View full text Add to dashboard Cite

Nine human tumour cell lines (four mammary, one bladder, two prostate, one cervical, and one squamous cell carcinoma) were studied as to whether cellular radiosensitivity is related to the number of initial or residual double-strand breaks (dsb). Cellular sensitivity was measured by colony assay and dsb by means of constant-and graded-field gel electrophoresis (CFGE and GFGE, respectively). The nine tumour cell lines showed a broad variation in cellular sensitivity (SF2 0.17 -0.63). The number of initial dsb as measured by GFGE ranged between 14 and 27 dsb/Gy/diploid DNA content. In contrast, normal fibroblasts raised from skin biopsies of seven individuals showed only a marginal variation with 18 -20 dsb/Gy/diploid DNA content. For eight of the nine tumour cell lines, there was a significant correlation between the number of initial dsb and the cellular radiosensitivity. The tumour cells showed a broad variation in the amount of dsb measured 24 h after irradiation by CFGE, which, however, was not correlated with the cellular sensitivity. This residual damage was found to be influenced not only by the actual number of residual dsb, but also by apoptosis and cell cycle progression which had impact on CFGE measurements. Some cell line strains were able to proliferate even after exposure to 150 Gy while others were found to degrade their DNA. Our results suggest that for tumour cells, in contrast to normal cells, the variation in sensitivity is mainly determined by differences in the initial number of dsb induced.

show abstract

DNA Damage Produced by Ionizing Radiation in Mammalian Cells: Identities, Mechanisms of Formation, and Reparability

Cited by 1,311 publications

References 58 publications

Potential use of the alkaline comet assay as a predictor of bladder tumour response to radiation

Potential use of the alkaline comet assay as a predictor of bladder tumour response to radiation

Measurements using the alkaline comet assay predict bladder cancer cell radiosensitivity

Radiosensitivity of human tumour cells is correlated with the induction but not with the repair of DNA double-strand breaks

Contact Info

Product

Resources

About