Increased repair and cell survival in cells treated with DIR1 antisense oligonucleotides: implications for induced radioresistance

T Robson, ME Price, ML Moore, MC Joiner, Valerie McKelvey-Martin, Stephanie McKeown, DG Hirst

    Research output: Contribution to journalArticle

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    Abstract

    Purpose: To determine whether repression of a recently isolated, X-ray-responsive gene, DIR1, using antisense oligonucleotides could affect clonogenic cell survival and repair of DNA strand breaks and have a possible role in the mechanism underlying the phenomenon of `induced radioresistance' (IRR). Materials and methods: Three cell lines, V79, RT112 and UM-UC-3, which are known to exhibit low-dose hypersensitivity (HRS) and induced radioresistance (IRR), and the radiosensitive cell line ATBIVA, were transfected with antisense oligonucleotides directed towards the DIR1 gene. Scrambled oligonucleotides were used as controls. DNA single-strand break (ssb) repair, using the alkaline comet assay, and cell survival using a standard clonogenic assay was measured after exposure to S-rays. Results: Following treatment with 4 Gy X-rays, the V79, RT112 and UM-UC-3 cell lines all exhibited significantly increased rates of ssb repair after transfection with DIR1 antisense oligonucleotides compared with cells transfected with scrambled oligonucleotides. They also demonstrated significantly enhanced survival after exposure to 2 Gy X-rays; the radiosensitive ATBIVA cells did not show these effects. Conclusions: Repression of the DIR1 gene product leads to an increase in the rate of repair and cell survival in three radioresistant cells lines but not in the radiosensitive ATBIVA cell line. Because DIR1 is repressed by S-rays in the dose range where IRR is observed, it may represent a candidate gene involved in the IRR phenomenon.
    LanguageEnglish
    Pages617-623
    JournalInternational Journal of Radiation Biology
    Volume76
    Issue number5
    Publication statusPublished - May 2000

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    Antisense Oligonucleotides
    Cell Survival
    Cell Line
    X-Rays
    Oligonucleotides
    Genes
    Single-Stranded DNA Breaks
    DNA Breaks
    Comet Assay
    Transfection
    Hypersensitivity

    Cite this

    Robson, T., Price, ME., Moore, ML., Joiner, MC., McKelvey-Martin, V., McKeown, S., & Hirst, DG. (2000). Increased repair and cell survival in cells treated with DIR1 antisense oligonucleotides: implications for induced radioresistance. International Journal of Radiation Biology, 76(5), 617-623.
    Robson, T ; Price, ME ; Moore, ML ; Joiner, MC ; McKelvey-Martin, Valerie ; McKeown, Stephanie ; Hirst, DG. / Increased repair and cell survival in cells treated with DIR1 antisense oligonucleotides: implications for induced radioresistance. In: International Journal of Radiation Biology. 2000 ; Vol. 76, No. 5. pp. 617-623.
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    title = "Increased repair and cell survival in cells treated with DIR1 antisense oligonucleotides: implications for induced radioresistance",
    abstract = "Purpose: To determine whether repression of a recently isolated, X-ray-responsive gene, DIR1, using antisense oligonucleotides could affect clonogenic cell survival and repair of DNA strand breaks and have a possible role in the mechanism underlying the phenomenon of `induced radioresistance' (IRR). Materials and methods: Three cell lines, V79, RT112 and UM-UC-3, which are known to exhibit low-dose hypersensitivity (HRS) and induced radioresistance (IRR), and the radiosensitive cell line ATBIVA, were transfected with antisense oligonucleotides directed towards the DIR1 gene. Scrambled oligonucleotides were used as controls. DNA single-strand break (ssb) repair, using the alkaline comet assay, and cell survival using a standard clonogenic assay was measured after exposure to S-rays. Results: Following treatment with 4 Gy X-rays, the V79, RT112 and UM-UC-3 cell lines all exhibited significantly increased rates of ssb repair after transfection with DIR1 antisense oligonucleotides compared with cells transfected with scrambled oligonucleotides. They also demonstrated significantly enhanced survival after exposure to 2 Gy X-rays; the radiosensitive ATBIVA cells did not show these effects. Conclusions: Repression of the DIR1 gene product leads to an increase in the rate of repair and cell survival in three radioresistant cells lines but not in the radiosensitive ATBIVA cell line. Because DIR1 is repressed by S-rays in the dose range where IRR is observed, it may represent a candidate gene involved in the IRR phenomenon.",
    author = "T Robson and ME Price and ML Moore and MC Joiner and Valerie McKelvey-Martin and Stephanie McKeown and DG Hirst",
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    Robson, T, Price, ME, Moore, ML, Joiner, MC, McKelvey-Martin, V, McKeown, S & Hirst, DG 2000, 'Increased repair and cell survival in cells treated with DIR1 antisense oligonucleotides: implications for induced radioresistance', International Journal of Radiation Biology, vol. 76, no. 5, pp. 617-623.

    Increased repair and cell survival in cells treated with DIR1 antisense oligonucleotides: implications for induced radioresistance. / Robson, T; Price, ME; Moore, ML; Joiner, MC; McKelvey-Martin, Valerie; McKeown, Stephanie; Hirst, DG.

    In: International Journal of Radiation Biology, Vol. 76, No. 5, 05.2000, p. 617-623.

    Research output: Contribution to journalArticle

    TY - JOUR

    T1 - Increased repair and cell survival in cells treated with DIR1 antisense oligonucleotides: implications for induced radioresistance

    AU - Robson, T

    AU - Price, ME

    AU - Moore, ML

    AU - Joiner, MC

    AU - McKelvey-Martin, Valerie

    AU - McKeown, Stephanie

    AU - Hirst, DG

    PY - 2000/5

    Y1 - 2000/5

    N2 - Purpose: To determine whether repression of a recently isolated, X-ray-responsive gene, DIR1, using antisense oligonucleotides could affect clonogenic cell survival and repair of DNA strand breaks and have a possible role in the mechanism underlying the phenomenon of `induced radioresistance' (IRR). Materials and methods: Three cell lines, V79, RT112 and UM-UC-3, which are known to exhibit low-dose hypersensitivity (HRS) and induced radioresistance (IRR), and the radiosensitive cell line ATBIVA, were transfected with antisense oligonucleotides directed towards the DIR1 gene. Scrambled oligonucleotides were used as controls. DNA single-strand break (ssb) repair, using the alkaline comet assay, and cell survival using a standard clonogenic assay was measured after exposure to S-rays. Results: Following treatment with 4 Gy X-rays, the V79, RT112 and UM-UC-3 cell lines all exhibited significantly increased rates of ssb repair after transfection with DIR1 antisense oligonucleotides compared with cells transfected with scrambled oligonucleotides. They also demonstrated significantly enhanced survival after exposure to 2 Gy X-rays; the radiosensitive ATBIVA cells did not show these effects. Conclusions: Repression of the DIR1 gene product leads to an increase in the rate of repair and cell survival in three radioresistant cells lines but not in the radiosensitive ATBIVA cell line. Because DIR1 is repressed by S-rays in the dose range where IRR is observed, it may represent a candidate gene involved in the IRR phenomenon.

    AB - Purpose: To determine whether repression of a recently isolated, X-ray-responsive gene, DIR1, using antisense oligonucleotides could affect clonogenic cell survival and repair of DNA strand breaks and have a possible role in the mechanism underlying the phenomenon of `induced radioresistance' (IRR). Materials and methods: Three cell lines, V79, RT112 and UM-UC-3, which are known to exhibit low-dose hypersensitivity (HRS) and induced radioresistance (IRR), and the radiosensitive cell line ATBIVA, were transfected with antisense oligonucleotides directed towards the DIR1 gene. Scrambled oligonucleotides were used as controls. DNA single-strand break (ssb) repair, using the alkaline comet assay, and cell survival using a standard clonogenic assay was measured after exposure to S-rays. Results: Following treatment with 4 Gy X-rays, the V79, RT112 and UM-UC-3 cell lines all exhibited significantly increased rates of ssb repair after transfection with DIR1 antisense oligonucleotides compared with cells transfected with scrambled oligonucleotides. They also demonstrated significantly enhanced survival after exposure to 2 Gy X-rays; the radiosensitive ATBIVA cells did not show these effects. Conclusions: Repression of the DIR1 gene product leads to an increase in the rate of repair and cell survival in three radioresistant cells lines but not in the radiosensitive ATBIVA cell line. Because DIR1 is repressed by S-rays in the dose range where IRR is observed, it may represent a candidate gene involved in the IRR phenomenon.

    M3 - Article

    VL - 76

    SP - 617

    EP - 623

    JO - International Journal of Radiation Biology

    T2 - International Journal of Radiation Biology

    JF - International Journal of Radiation Biology

    SN - 0955-3002

    IS - 5

    ER -