DNA Double-strand Break Repair and Radiation Response in Human Tumour Primary Cultures

Zaffaroni, Nadia; Orlandi, L.; Villa, Riccardo; Bearzatto, A.; Rofstad, Einar K.; Silvestrini, Rosella

doi:10.1080/09553009414551211

Cited by 32 publications

(16 citation statements)

References 26 publications

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“…For the nine tumuor cell lines tested, the number of dsb induced was found to vary by a factor of 2 from 5.75 to 11.0 Â 10 À12 dsb/Gy/ Da (Table 2), which in principle agreed with most previous studies (Kelland et al, 1988;McMillan et al, 1990;Schwartz et al, 1990Schwartz et al, , 1991Ruiz de Almodovar et al, 1994;Zaffaroni et al, 1994;Whitaker et al, 1995;Woudstra et al, 1998;Eastham et al, 2001) using either PFGE or neutral filter elution. Some authors did not mention differences in particular; however, variations were in the same order of magnitude as the above reports (Giaccia et al, 1992;Olive et al, 1994;McKay and Kefford, 1995).…”

Section: Relationship Between Induced Damage and Cellular Radiosensitsupporting

confidence: 89%

“…11 out of 13 studies reported on a variation in the number of induced dsb (Kelland et al, 1988;Schwartz et al, 1988Schwartz et al, , 1990Schwartz et al, , 1991McMillan et al, 1990;Giaccia et al, 1992;Olive et al, 1994;Ruiz de Almodovar et al, 1994;Zaffaroni et al, 1994;McKay and Kefford, 1995;Whitaker et al, 1995;Woudstra et al, 1998;Eastham et al, 2001), but only three found a correlation with cell killing (McMillan et al, 1990;Ruiz de Almodovar et al, 1994;Whitaker et al, 1995). In repair studies, a correlation between cell killing and the number of dsb was only found after short repair intervals (up to 2 h) (Schwartz et al, 1988(Schwartz et al, , 1990Giaccia et al, 1992;Zaffaroni et al, 1994), but never for nonreparable dsb.…”

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confidence: 99%

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

2003

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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.

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Section: Relationship Between Induced Damage and Cellular Radiosensitsupporting

confidence: 89%

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confidence: 99%

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

2003

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“…A period of 3 (CAM) or 4 (soft agar) weeks is required to generate data, and success rates in obtaining results are only around 70%. More rapid assays are being studied for their potential use in clinical studies: in particular the calorimetric microtitre (MTT) assay (Ramsay et al, 1992), the micronucleus assay (Zolzer et al, 1995), fluorescence in situ hybridization (Coco-Martin et al, 1994) and assays of DNA double-strand break repair (Zaffaroni et al, 1994;Schwartz et al, 1996). Alongside this interest in evaluating the potential of rapid assays of tumour radiosensitivity, there is a need to show, within large prospective clinical studies, whether there is a future for radiosensitivity testing in cancers treated with radiotherapy alone or in combination with surgery.…”

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confidence: 99%

The in vitro radiosensitivity of human head and neck cancers

Björk‐Eriksson

West²,

Karlsson³

et al. 1998

Br J Cancer

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Summary A study was made of the intrinsic radiosensitivity of 140 biopsy and surgical specimens of malignant head and neck tumours of different histologies. Using a soft-agar clonogenic assay, the material was assessed for the ability to grow in culture (colony-forming efficiency; CFE) and inherent tumour radiosensitivity (surviving fraction at 2 Gy, SF2). The success rate for obtaining growth was 74% (104/140) with a mean CFE of 0.093% (median 0.031) and a range of 0.002-1.3%. SF2 was obtained for 88 of 140 specimens, representing a success rate of 63% with a mean SF2 of 0.48 (median 0.43) and a range of 0.10-1.00. There were no significant differences in radiosensitivity between different sites of the head and neck region. There were no significant relationships between SF2 and disease stage, nodal status, tumour grade, patient age, primary tumour growth pattern and CFE. The results were compared with those for other tumour types previously analysed with the same assay. The distribution of the SF2 values for the head and neck tumours was similar to that for 145 cervix carcinomas and there was no significant difference in mean radiosensitivity between the two tumour types. Also, there was no significant difference in radiosensitivity between head and neck tumours and either breast or colorectal cancers. However, a group of eight lymphomas was significantly more radiosensitive. These results confirm the feasibility of carrying out radiosensitivity measurements using a soft-agar clonogenic assay on head and neck tumours. In addition, the work has shown that radiosensitivity is independent of many clinical parameters and that the mean value is similar to that reported for cervix carcinomas.

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“…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. Nevertheless other human tumour studies measuring DNA dsbs by asymmetric field-inversion gel electrophoresis (Giaccia et al, 1992) and neutral filter elution (Zaffaroni et al, 1994) have indeed shown significant correlations between the level of residual dsbs and radiosensitivity.…”

Section: Discussionmentioning

confidence: 95%

“…A number of reports indicate that tumour cell radiosensitivity is positively correlated with the levels of initial radiation-induced DNA dsbs (Kelland et al, 1988;Peacock et al, 1989;McMillan et al, 1990;Ruiz de Almodovar et al, 1994), while others have shown no correlation (Smeets et al, 1993;Olive et al, 1994;McKay and Kefford, 1995). Positive correlations between tumour cell radiosensitivity and the extent of residual DNA dsbs (Giaccia et al, 1992;Zaffaroni et al, 1994), the rate of DNA dsb repair (Schwartz et al, 1988) and the misrepair of radiation-induced DNA damage (Powell et al, 1992;Powell and McMillan, 1994) have also been reported.…”

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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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DNA Double-strand Break Repair and Radiation Response in Human Tumour Primary Cultures

Cited by 32 publications

References 26 publications

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

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

The in vitro radiosensitivity of human head and neck cancers

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

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