DNA interstrand cross-linking upon irradiation of aryl halide C-nucleotides.

ABSTRACT: γ-Radiolysis kills cells by damaging DNA via radical processes. Many of the radical pathways are O2 dependent, which results in a reduction in the cytotoxicity of ionizing radiation in hypoxic tumor cells. Consequently, there is a need for chemical agents that increase DNA damage by ionizing radiation under O2-deficient conditions. Modified nucleotides that are incorporated in DNA and produce highly reactive σ-radicals are useful as radiosensitizing agents. Aryl halide C-nucleotides (4-6) were incorporated into oligonucleotides by solid-phase synthesis. Duplex DNA containing 4-6 forms interstrand cross-links upon γ-radiolysis under anaerobic conditions or UV irradiation. Deep Vent (exo(-)) DNA polymerase accepted the nucleotide triphosphate of C-nucleotide 6 as a substrate and preferential

SUBMITTER: Hou D 

PROVIDER: S-EPMC3982193 | biostudies-literature | 2014 Mar

REPOSITORIES: biostudies-literature