The radioresponsiveness of human tumours and the initial slope ofthe cell survival curve

Deacon, Judith; Peckham, M. J.; Steel, G. Gordon

doi:10.1016/s0167-8140(84)80074-2

Cited by 450 publications

(137 citation statements)

References 16 publications

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“…Clearly, for some tumours the wrong conclusion could be arrived at if radiosensitivity is predicted using a dose, even a few Gy, above that used in the clinic. This conclusion also concurs with seminal studies of Malaise et al (1987) and Deacon et al (1984), updated by Steel (1996) in which they provide considerable evidence that the radiosensitivity of tumours is most reliably measured at 2 Gy. The clinical studies of West and colleagues would support this proposition (West et al, 1997;Bjork-Eriksson et al, 2000).…”

Section: Discussionsupporting

confidence: 89%

“…However, a number of factors can influence cell survival following radiation exposure, and the studies of Malaise et al (1987) and Deacon et al (1984) suggest that for a predictive test of radiosensitivity the measurements must be made at doses o6 Gy. Therefore studies of DSBs, although useful in understanding physico-chemical effects of radiation on DNA, have less utility in defining clinically relevant parameters.…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2003

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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.

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Section: Discussionsupporting

confidence: 89%

Section: Discussionmentioning

confidence: 99%

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

et al. 2003

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“…Focusing on the last parameter the surviving fraction at 2 Gy (SF2) of human tumour cell lines has been shown to correlate with the radioresponsiveness of the tumour types from which they were derived (Deacon et al, 1984;Fertil and Malaise, 1985). The predictive value of parameters of the low-dose region of radiation cell survival curves has also been confirmed by studies on experimental animal tumours (Bristow and Hill, 1990) and in mathematical modelling systems (Tucker and Thames, 1989).…”

mentioning

confidence: 89%

“…tests. However, intrinsic radiosensitivity expressed as parameters of the low-dose region of radiation cell survival curves is thought to be one of the most important and significant factors determining the response of a tumour to radiation treatment (Deacon et al, 1984;Fertil and Malaise, 1985;Tucker and Thames, 1989;Brock et al, 1990Brock et al, , 1992Davidson et al, 1990;West and Hendry 1992;West et al, 1993West et al, , 1997Girinsky et al, 1993Girinsky et al, , 1994.…”

Section: Sf2mentioning

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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“…Intrinsic cellular radiosensitivity is now widely recognized as a significant factor influencing the clinical response of tumours (Fertil and Malaise, 1981; Deacon et al, 1984) and normal tissues (Burnet et al, 1992;Wurm et al, 1995) to ionizing radiation. Certain radiobiological parameters have been implicated as important determinants of the degree of intrinsic radiosensitivity shown by different cells.…”

mentioning

confidence: 99%

Late G1 accumulation after 2 Gy of γ-irradiation is related to endogenous Raf-1 protein expression and intrinsic radiosensitivity in human cells

Warenius

Jones²,

Jones³

et al. 1998

Br J Cancer

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Summary We have previously reported a correlation between high endogenous expression of the protein product of the RAF-1 protooncogene, intrinsic cellular radiosensitivity and rapid exit from a G/M delay induced by 2 Gy of y-irradiation. Rafl is a positive serine/threonine kinase signal transduction factor that relays signals from the cell membrane to the MAP kinase system further downstream and is believed to be involved in an ionizing radiation signal transduction pathway modulating the G /S checkpoint. We therefore extended our flow cytometric studies to investigate relationships between radiosensitivity, endogenous expression of the Rafl protein and perturbation of cell cycle checkpoints, leading to alterations in the G1, S and G/M populations after 2 Gy of y-irradiation. Differences in intrinsic radiosensitivity after modulation of the GW/S checkpoint have generally been understood to involve p53 function up to the present time. A role for dominant oncogenes in control of G1/S transit in radiation-treated cells has not been identified previously. Here, we show in 12 human in vitro cancer cell lines that late G1 accumulation after 2 Gy of radiation is related to both Rafl expression (r = 0.91, P = 0.0001) and the radiosensitivity parameter SF2 (r = -0.71, P = 0.009).

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The radioresponsiveness of human tumours and the initial slope ofthe cell survival curve

Cited by 450 publications

References 16 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

The in vitro radiosensitivity of human head and neck cancers

Late G1 accumulation after 2 Gy of γ-irradiation is related to endogenous Raf-1 protein expression and intrinsic radiosensitivity in human cells

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