The production of DNA double-strand breaks (DSBs) was studied in cells of four CHO cell lines under conditions where combining radiation with carboplatin enhanced cell killing (radiosensitization and radiopotentiation). The cell lines included repair-proficient (AA8 and K1), excision repair-deficient (UV41) and DSB repair-deficient (xrs-5) cells. Double-strand breaks were analyzed by neutral elution either immediately after or 4 h after a single 55-Gy radiation dose delivered under hypoxic conditions. Carboplatin (1 mM) combined with radiation produced a small increase in DSBs compared to radiation alone immediately after irradiation in AA8, UV41 and xrs-5 cells. However, the yield of DSBs in AA8, K1 and xrs-5 cells was significantly higher 4 h after carboplatin-radiation treatment; no such increase was found at 4 h in UV41 cells. Strand scission factors (SSFs) were calculated as SSF = -log [percentage DNA remaining on filter at 8 h elution (treated cells)/percentage DNA remaining at 8 h elution (untreated cells)]. The ratios of the SSF at 4 h to 0 h postirradiation for carboplatin-treated cells were 13.7 for K1, 4.9 for xrs-5, 2.5 for AA8 and 1.2 for UV41 cells. These results support a possible explanation for the enhanced killing of irradiated cells by platinum chemotherapeutic agents, namely enhanced production of DSBs.
Production of DNA Double-Strand Breaks by Interactions between Carboplatin and Radiation: A Potential Mechanism for Radiopotentiation
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Li-xi Yang, Evan B. Douple, Julia A. O'Hara, Hui-Juan Wang; Production of DNA Double-Strand Breaks by Interactions between Carboplatin and Radiation: A Potential Mechanism for Radiopotentiation. Radiat Res 1 September 1995; 143 (3): 309–315. doi: https://doi.org/10.2307/3579218
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