Abstract
DNA damage and repair is a fundamental process that plays an important role in cancer treatment. Base excision repair (BER) is a major repair pathway that often leads to drug resistance in DNA-targeted cancer chemotherapy. In order to measure BER, we have developed a near infrared (NIR) fluorescent probe. This probe binds to a key intermediate, termed apurinic/apyrimidinic (AP) site, in the BER pathway where DNA damage and repair occurs. We have developed an assay to show the efficacy of the probe binding to AP sites and have shown that it can distinguish AP sites in DNA extract from chemotherapy treated cells. This probe has potential application in monitoring patient response to chemotherapy and evaluating new drugs in development.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Base Pairing
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Base Sequence
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Binding Sites
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Cattle
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Cell Line, Tumor
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Colonic Neoplasms / pathology
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DNA / metabolism
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DNA Breaks, Single-Stranded
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DNA Damage*
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DNA Repair* / drug effects
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DNA-(Apurinic or Apyrimidinic Site) Lyase / metabolism
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Floxuridine / pharmacology
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Fluorescent Dyes / chemical synthesis
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Fluorescent Dyes / chemistry
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Fluorescent Dyes / metabolism*
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Humans
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Hydroxylamines / metabolism
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Methyl Methanesulfonate / pharmacology
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Molecular Sequence Data
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Spectrometry, Fluorescence
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Time Factors
Substances
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Fluorescent Dyes
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Hydroxylamines
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Floxuridine
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DNA
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calf thymus DNA
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methoxyamine
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Methyl Methanesulfonate
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DNA-(Apurinic or Apyrimidinic Site) Lyase