Irradiation-enhanced Binding of Carboplatin to DNA

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Abstract
Carboplatin (3·6 mm) and salmon sperm DNA (3 µg), either double-stranded (dsDNA) or denatured single-stranded (ssDNA), were irradiated (100 Gy) under hypoxic or oxic conditions. The drug and DNA were mixed either before, during, or after irradiation, and platinum binding to DNA was measured using atomic absorption spectrometry. Irradiation significantly increased the binding of carboplatin to dsDNA under hypoxic conditions, but did not increase the binding of carboplatin to ssDNA under similar hypoxic conditions. Irradiation did not result in an increased dsDNA–platinum binding under oxic conditions. When carboplatin was added to dsDNA immediately following irradiation of dsDNA, no increase in platinum binding was observed. When carboplatin and dsDNA were irradiated simultaneously but separately and then mixed there appears to be a slight increase in platinum binding, but it was not significant. Tetra-ammineplatinum (II) chloride, a non-cytotoxic platinum compound, did not show an increase in platinum–DNA binding following irradiation under hypoxic conditions. The results suggest that radiation-enhanced carboplatin binding to DNA might be at least partly responsible for radiosensitization by carboplatin, especially in a cell line sensitive to carboplatin.