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Background: Gimeracil (CDHP; 5-chloro-2, 4-dihydroxypyridine) is a component of S-1, which is a novel chemotherapeutic agent [composed of tegafur (a prodrug of 5-FU), CDHP that inhibits degradation of 5-FU, and oxonate that regulates the phosphorylation of 5-FU in the gastrointestinal tract to reduce the adverse effects] and has increasingly been used for the treatment of human cancer including gastrointestinal carcinomas. In these components, CDHP and oxonate has no antitumor activity and no toxicity by itself. But recently we found that CDHP showed a radiosensitizing effect and combined with radiation showing a great antitumor efficacy. In this study we report the efficacy of CDHP as a radiosensitizer from in vivo and in vitro experiments. Materials and methods: whether CDHP enhances the therapeutic efficacy of radiation, we inoculated DLD-1/FU human colon cancer cell xenografts in nude mice. when tumor grow 80mm3, mice were treated with 5 Gy , 2 times (day 1 and 8 ) local tumor irradiation, 25 mg/kg CDHP given to mice orally once daily for 14 consecutive days, or with both. In the combined group CDHP administration was begun 1 h before irradiation. Tumor growth delay was the treatments’ endpoint. During the experiment, mice weight was also measured to check the toxicity. To determine whether CDHP enhances intrinsic cell radiosensitivity, DLD-1/FU cells were incubated with 150 or 200μM CDHP for 1 or 2 days and exposed to 1 to 6 Gy single-dose of X-rays. Then clonogenic cell survival were assessed. Result: The Growth delay experiment showed that while CDHP or XRT were only slightly effective as single agents in delaying tumor growth, the combined treatment was highly effective. The CDHP treatment increased the efficacy of local tumor irradiation by a factor of 1.87. And weight curve showed that treatment with CDHP, the weight decrease ratio was fewer than that of non-CDHP treatment. In vitro clonogenic cell survival assay showed that CDHP strongly enhanced cell radiosensitivity, by a factor of 1.48 (150μM 1and 2 days), 1.79 (200μM 1day) at the 0.1 cell survival level. CDHP reduced the shoulder region on the radiation cell survival curve suggesting that the drug might have impaired cellular repair from sublethal radiation damage. Conclusions: Combined CDHP plus radiation treatment resulted in a synergistic effect for therapy of a DLD-1/FU tumor. The effect could be attributed to the ability of CDHP to increase cell radiosensitivity. Regarding these deta and low toxicity, we conclude that CDHP may be a great radioenhancer drug.

98th AACR Annual Meeting-- Apr 14-18, 2007; Los Angeles, CA