Relationship between clonogenic radiosensitivity, radiation-induced apoptosis and DNA damage/repair in human colon cancer cells

AL Dunne, ME Price, C Mothersill, Stephanie McKeown, T Robson, DG Hirst

    Research output: Contribution to journalArticle

    62 Citations (Scopus)

    Abstract

    The intrinsic radiation sensitivity of normal and tumour tissue is a major determinant of the outcome of radiotherapy. There is currently no established test that can be used routinely to measure the radiosensitivity of the cells in an individual patient's cancer in a manner that can inform treatment planning. The purpose of this study was to evaluate, in four human colorectal adenocarcinoma cell lines, two possible end points as surrogate markers of radiation response - apoptosis and induction of DNA single-strand breaks - and to compare the results with those of a conventional clonogenic assay. Cell lines (SW707 SW480, SW48 and HT29) known to differ in radiosensitivity were exposed to single doses of X-rays ranging from 0.5 to 5 Gy and cell survival was measured using the clonogenic assay. Apoptosis was determined on the basis of morphology under fluorescent microscopy and DNA damage/repair was measured, as tail moment, using an adaptation of the alkaline comet assay. The relationship between surviving fraction at 2 Gy (SF2) and the percentage of apoptotic cells 24 h after the same dose was complex, but apoptosis accurately predicted the order of radiosensitivities as measured by SF2. Initial damage measured after 2 Gy using the alkaline comet assay gave a close correlation with SF2 (r(2)=0.95), whereas there was no correlation between initial DNA damage repair rate and SF2.
    LanguageEnglish
    Pages2277-2283
    JournalBRITISH JOURNAL OF CANCER
    Volume89
    Issue number12
    DOIs
    Publication statusPublished - Dec 2003

    Fingerprint

    Radiation Tolerance
    DNA Repair
    Colonic Neoplasms
    DNA Damage
    Radiation
    Apoptosis
    Comet Assay
    Single-Stranded DNA Breaks
    Cell Line
    Tail
    Microscopy
    Neoplasms
    Cell Survival
    Adenocarcinoma
    Radiotherapy
    Biomarkers
    X-Rays
    Therapeutics

    Cite this

    Dunne, AL ; Price, ME ; Mothersill, C ; McKeown, Stephanie ; Robson, T ; Hirst, DG. / Relationship between clonogenic radiosensitivity, radiation-induced apoptosis and DNA damage/repair in human colon cancer cells. In: BRITISH JOURNAL OF CANCER. 2003 ; Vol. 89, No. 12. pp. 2277-2283.
    @article{8ff68851b4364a48823851b4f8a4ecaa,
    title = "Relationship between clonogenic radiosensitivity, radiation-induced apoptosis and DNA damage/repair in human colon cancer cells",
    abstract = "The intrinsic radiation sensitivity of normal and tumour tissue is a major determinant of the outcome of radiotherapy. There is currently no established test that can be used routinely to measure the radiosensitivity of the cells in an individual patient's cancer in a manner that can inform treatment planning. The purpose of this study was to evaluate, in four human colorectal adenocarcinoma cell lines, two possible end points as surrogate markers of radiation response - apoptosis and induction of DNA single-strand breaks - and to compare the results with those of a conventional clonogenic assay. Cell lines (SW707 SW480, SW48 and HT29) known to differ in radiosensitivity were exposed to single doses of X-rays ranging from 0.5 to 5 Gy and cell survival was measured using the clonogenic assay. Apoptosis was determined on the basis of morphology under fluorescent microscopy and DNA damage/repair was measured, as tail moment, using an adaptation of the alkaline comet assay. The relationship between surviving fraction at 2 Gy (SF2) and the percentage of apoptotic cells 24 h after the same dose was complex, but apoptosis accurately predicted the order of radiosensitivities as measured by SF2. Initial damage measured after 2 Gy using the alkaline comet assay gave a close correlation with SF2 (r(2)=0.95), whereas there was no correlation between initial DNA damage repair rate and SF2.",
    author = "AL Dunne and ME Price and C Mothersill and Stephanie McKeown and T Robson and DG Hirst",
    year = "2003",
    month = "12",
    doi = "10.1038/sj.bjc.6601427",
    language = "English",
    volume = "89",
    pages = "2277--2283",
    journal = "BRITISH JOURNAL OF CANCER",
    issn = "0007-0920",
    number = "12",

    }

    Relationship between clonogenic radiosensitivity, radiation-induced apoptosis and DNA damage/repair in human colon cancer cells. / Dunne, AL; Price, ME; Mothersill, C; McKeown, Stephanie; Robson, T; Hirst, DG.

    In: BRITISH JOURNAL OF CANCER, Vol. 89, No. 12, 12.2003, p. 2277-2283.

    Research output: Contribution to journalArticle

    TY - JOUR

    T1 - Relationship between clonogenic radiosensitivity, radiation-induced apoptosis and DNA damage/repair in human colon cancer cells

    AU - Dunne, AL

    AU - Price, ME

    AU - Mothersill, C

    AU - McKeown, Stephanie

    AU - Robson, T

    AU - Hirst, DG

    PY - 2003/12

    Y1 - 2003/12

    N2 - The intrinsic radiation sensitivity of normal and tumour tissue is a major determinant of the outcome of radiotherapy. There is currently no established test that can be used routinely to measure the radiosensitivity of the cells in an individual patient's cancer in a manner that can inform treatment planning. The purpose of this study was to evaluate, in four human colorectal adenocarcinoma cell lines, two possible end points as surrogate markers of radiation response - apoptosis and induction of DNA single-strand breaks - and to compare the results with those of a conventional clonogenic assay. Cell lines (SW707 SW480, SW48 and HT29) known to differ in radiosensitivity were exposed to single doses of X-rays ranging from 0.5 to 5 Gy and cell survival was measured using the clonogenic assay. Apoptosis was determined on the basis of morphology under fluorescent microscopy and DNA damage/repair was measured, as tail moment, using an adaptation of the alkaline comet assay. The relationship between surviving fraction at 2 Gy (SF2) and the percentage of apoptotic cells 24 h after the same dose was complex, but apoptosis accurately predicted the order of radiosensitivities as measured by SF2. Initial damage measured after 2 Gy using the alkaline comet assay gave a close correlation with SF2 (r(2)=0.95), whereas there was no correlation between initial DNA damage repair rate and SF2.

    AB - The intrinsic radiation sensitivity of normal and tumour tissue is a major determinant of the outcome of radiotherapy. There is currently no established test that can be used routinely to measure the radiosensitivity of the cells in an individual patient's cancer in a manner that can inform treatment planning. The purpose of this study was to evaluate, in four human colorectal adenocarcinoma cell lines, two possible end points as surrogate markers of radiation response - apoptosis and induction of DNA single-strand breaks - and to compare the results with those of a conventional clonogenic assay. Cell lines (SW707 SW480, SW48 and HT29) known to differ in radiosensitivity were exposed to single doses of X-rays ranging from 0.5 to 5 Gy and cell survival was measured using the clonogenic assay. Apoptosis was determined on the basis of morphology under fluorescent microscopy and DNA damage/repair was measured, as tail moment, using an adaptation of the alkaline comet assay. The relationship between surviving fraction at 2 Gy (SF2) and the percentage of apoptotic cells 24 h after the same dose was complex, but apoptosis accurately predicted the order of radiosensitivities as measured by SF2. Initial damage measured after 2 Gy using the alkaline comet assay gave a close correlation with SF2 (r(2)=0.95), whereas there was no correlation between initial DNA damage repair rate and SF2.

    U2 - 10.1038/sj.bjc.6601427

    DO - 10.1038/sj.bjc.6601427

    M3 - Article

    VL - 89

    SP - 2277

    EP - 2283

    JO - BRITISH JOURNAL OF CANCER

    T2 - BRITISH JOURNAL OF CANCER

    JF - BRITISH JOURNAL OF CANCER

    SN - 0007-0920

    IS - 12

    ER -