We have reported that ascorbate radical (Asc·-) could serve as an indicator of the amount of hydroxyl radical and superoxide produced by irradiation in vivo. Using this method, we investigated the relationship between tumor size and Asc·- production after irradiation (10 Gy) and between tumor size and the radical-scavenging ability of WR-2721 (300 mg/kg). Asc·- was measured in normal muscle and SCC-VII tumors transplanted into mice (n = 6). In tumors, the increase in Asc·- significantly decreased with increasing tumor size (r = -0.483; P < 0.05). The increase in Asc·- production after irradiation was more inhibited by WR-2721 in normal muscle tissue than in tumor tissue at various sizes. In tumors, the increase in Asc·- was less inhibited by WR-2721 with increasing tumor size. These results demonstrate that the increase in radical production after irradiation and drug distribution decreased with increasing tumor size and that WR-2721 has excellent differential protection. This method is expected to measure changes in the amounts of local hydroxyl radical and superoxide modified by a change of tumor environment or drug administration.

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