Induction and rejoining of DNA double-strand breaks in bladder tumor cells

ME Price, Valerie McKelvey-Martin, T Robson, DG Hirst, Stephanie McKeown

    Research output: Contribution to journalArticle

    21 Citations (Scopus)

    Abstract

    The induction and rejoining of radiation-induced double-strand breaks (DSBs) in cells of six bladder tumor cell lines (T24, UM-UC3, TCC-SUP, RT112, J82, HT1376) were measured using the neutral comet assay. Radiation dose-response curves (0-60 Gy) showed damage (measured as mean tail moment) for five of the cell lines in the same rank order as cell survival (measured over 0-10 Gy), with the least damage in the most radioresistant cell line. Damage induction correlated well with clonogenic survival at high doses (SF10) for all six cell lines. At the clinically relevant dose of 2 Gy, correlation was good for four cell lines but poor for two (TCC-SUP and T24), The rejoining process had a fast and slow component for all cell lines. The rate of these two components of DNA repair did not correlate with cell survival. However, the time taken to reduce the amount of DNA damage to preirradiated control levels correlated positively with cell survival at 10 Gy but not 2 Gy; radioresistant cells rejoined the induced DSBs to preirradiation control levels more quickly than the radiosensitive cells. Although the results show good correlation between SF10 and DSBs for all six cell lines, the lack of correlation with SF2 for TCC-SUP and T24 cells would suggest that a predictive test should be carried out at the clinically relevant dose. At present the neutral comet assay cannot achieve this. (C) 2000 by Radiation Research Society.
    LanguageEnglish
    Pages788-794
    JournalRadiation Research
    Volume153
    Issue number6
    Publication statusPublished - Jun 2000

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    Double-Stranded DNA Breaks
    Urinary Bladder Neoplasms
    Cell Line
    Cell Survival
    Comet Assay
    Radiation
    Tumor Cell Line
    DNA Repair
    DNA Damage

    Cite this

    Price, ME., McKelvey-Martin, V., Robson, T., Hirst, DG., & McKeown, S. (2000). Induction and rejoining of DNA double-strand breaks in bladder tumor cells. Radiation Research, 153(6), 788-794.
    Price, ME ; McKelvey-Martin, Valerie ; Robson, T ; Hirst, DG ; McKeown, Stephanie. / Induction and rejoining of DNA double-strand breaks in bladder tumor cells. In: Radiation Research. 2000 ; Vol. 153, No. 6. pp. 788-794.
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    abstract = "The induction and rejoining of radiation-induced double-strand breaks (DSBs) in cells of six bladder tumor cell lines (T24, UM-UC3, TCC-SUP, RT112, J82, HT1376) were measured using the neutral comet assay. Radiation dose-response curves (0-60 Gy) showed damage (measured as mean tail moment) for five of the cell lines in the same rank order as cell survival (measured over 0-10 Gy), with the least damage in the most radioresistant cell line. Damage induction correlated well with clonogenic survival at high doses (SF10) for all six cell lines. At the clinically relevant dose of 2 Gy, correlation was good for four cell lines but poor for two (TCC-SUP and T24), The rejoining process had a fast and slow component for all cell lines. The rate of these two components of DNA repair did not correlate with cell survival. However, the time taken to reduce the amount of DNA damage to preirradiated control levels correlated positively with cell survival at 10 Gy but not 2 Gy; radioresistant cells rejoined the induced DSBs to preirradiation control levels more quickly than the radiosensitive cells. Although the results show good correlation between SF10 and DSBs for all six cell lines, the lack of correlation with SF2 for TCC-SUP and T24 cells would suggest that a predictive test should be carried out at the clinically relevant dose. At present the neutral comet assay cannot achieve this. (C) 2000 by Radiation Research Society.",
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    Price, ME, McKelvey-Martin, V, Robson, T, Hirst, DG & McKeown, S 2000, 'Induction and rejoining of DNA double-strand breaks in bladder tumor cells', Radiation Research, vol. 153, no. 6, pp. 788-794.

    Induction and rejoining of DNA double-strand breaks in bladder tumor cells. / Price, ME; McKelvey-Martin, Valerie; Robson, T; Hirst, DG; McKeown, Stephanie.

    In: Radiation Research, Vol. 153, No. 6, 06.2000, p. 788-794.

    Research output: Contribution to journalArticle

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    AU - Price, ME

    AU - McKelvey-Martin, Valerie

    AU - Robson, T

    AU - Hirst, DG

    AU - McKeown, Stephanie

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    N2 - The induction and rejoining of radiation-induced double-strand breaks (DSBs) in cells of six bladder tumor cell lines (T24, UM-UC3, TCC-SUP, RT112, J82, HT1376) were measured using the neutral comet assay. Radiation dose-response curves (0-60 Gy) showed damage (measured as mean tail moment) for five of the cell lines in the same rank order as cell survival (measured over 0-10 Gy), with the least damage in the most radioresistant cell line. Damage induction correlated well with clonogenic survival at high doses (SF10) for all six cell lines. At the clinically relevant dose of 2 Gy, correlation was good for four cell lines but poor for two (TCC-SUP and T24), The rejoining process had a fast and slow component for all cell lines. The rate of these two components of DNA repair did not correlate with cell survival. However, the time taken to reduce the amount of DNA damage to preirradiated control levels correlated positively with cell survival at 10 Gy but not 2 Gy; radioresistant cells rejoined the induced DSBs to preirradiation control levels more quickly than the radiosensitive cells. Although the results show good correlation between SF10 and DSBs for all six cell lines, the lack of correlation with SF2 for TCC-SUP and T24 cells would suggest that a predictive test should be carried out at the clinically relevant dose. At present the neutral comet assay cannot achieve this. (C) 2000 by Radiation Research Society.

    AB - The induction and rejoining of radiation-induced double-strand breaks (DSBs) in cells of six bladder tumor cell lines (T24, UM-UC3, TCC-SUP, RT112, J82, HT1376) were measured using the neutral comet assay. Radiation dose-response curves (0-60 Gy) showed damage (measured as mean tail moment) for five of the cell lines in the same rank order as cell survival (measured over 0-10 Gy), with the least damage in the most radioresistant cell line. Damage induction correlated well with clonogenic survival at high doses (SF10) for all six cell lines. At the clinically relevant dose of 2 Gy, correlation was good for four cell lines but poor for two (TCC-SUP and T24), The rejoining process had a fast and slow component for all cell lines. The rate of these two components of DNA repair did not correlate with cell survival. However, the time taken to reduce the amount of DNA damage to preirradiated control levels correlated positively with cell survival at 10 Gy but not 2 Gy; radioresistant cells rejoined the induced DSBs to preirradiation control levels more quickly than the radiosensitive cells. Although the results show good correlation between SF10 and DSBs for all six cell lines, the lack of correlation with SF2 for TCC-SUP and T24 cells would suggest that a predictive test should be carried out at the clinically relevant dose. At present the neutral comet assay cannot achieve this. (C) 2000 by Radiation Research Society.

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    Price ME, McKelvey-Martin V, Robson T, Hirst DG, McKeown S. Induction and rejoining of DNA double-strand breaks in bladder tumor cells. Radiation Research. 2000 Jun;153(6):788-794.