End-joining deficiency and radiosensitization induced by gemcitabine

JWG van Putten*, HJM Groea, K Smid, GJ Peters, HH Kampinga

*Corresponding author for this work

    Research output: Contribution to journalArticleAcademicpeer-review

    54 Citations (Scopus)

    Abstract

    The mechanism of radiosensitization by gemcitabine (2',2'-dinuoro-2'-deoxycytidine, dFdC) is not exactly known. We investigated the possible role of inhibition of the repair of DNA double-strand breaks by dFdC by measuring the extent of radiosensitization in different cell lines deficient and proficient in components of nonhomologous end-joining and in the parental cell lines. Different cell lines were incubated with 0.5 and 5 muM dFdC for 4 h. Cells deficient in DNA-dependent protein-kinase catalytic subunit (V3) showed sensitization similar to that of wild-type cells (AA8) and complemented cells (V3+YAC). Ku80-deficient cells (xrs5 and xrs6) showed even more radiosensitization by dFdC as compared with wild-type CHO-K1. However, Ku80-complemented cell lines (xrs5+huKu80 and xrs6+haKu80) did not show radiosensitization. The differences in dFdC-mediated radiosensitization were not attributable to different changes in deoxynucleotide triphosphate levels and cell cycle distribution. We conclude that a functional nonhomologous end-joining pathway is not required for dFdC-mediated radiosensitization.

    Original languageEnglish
    Pages (from-to)1585-1591
    Number of pages7
    JournalCancer Research
    Volume61
    Issue number4
    Publication statusPublished - 15-Feb-2001

    Keywords

    • PROTEIN-KINASE ACTIVITY
    • DOUBLE-STRAND BREAKS
    • DNA-REPAIR
    • V(D)J RECOMBINATION
    • CELL-CYCLE
    • CHEF ELECTROPHORESIS
    • SCID MUTATION
    • TUMOR-CELLS
    • IN-VITRO
    • 2',2'-DIFLUORO-2'-DEOXYCYTIDINE

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