Antitumor Effect of Difluoromethylornithine and UFT on Dimethylhydrazine-induced Colon Tumors in Rats

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  • TSUNODA Akira
    <I>Department of Surgery, Showa University School of Medicine</I>
  • SHIBUSAWA Miki
    <I>Department of Surgery, Showa University School of Medicine</I>
  • TSUNODA Yuko
    <I>Department of Surgery, Showa University School of Medicine</I>
  • YASUDA Naokuni
    <I>Department of Surgery, Showa University School of Medicine</I>
  • KOIKE Tadashi
    <I>Department of Surgery, Showa University School of Medicine</I>

Description

Effectiveness of difluoromethylornithine (DFMO) and UFT was investigated by using tumor volume doubling time in chemically induced colon cancer in rats. Forty male Sprague-Dawley rats received 20 mg/kg dimethylhydrazine (DMH) s.c. once weekly for 20 weeks to induce colon cancer. Then double contrast barium enema was performed and colon tumors were detected. Tumor volume was calculated from three diameters of tumors. The animals were divided into four groups that were subjected to the following treatment: none, DFMO alone, UFT alone, and combination of DFMO plus UFT. DFMO was offered as 1 % solution in drinking water. UFT was given at a dosage of 80 mg/kg/day. After five weeks treatment, barium enema was repeated. For the evaluation of treatment efficacy, tumor doubling time was adopted. Mean tumor doubling time in the control group was 12.0 days ±4.4 (m±SD) and more than 20.8 days (m+2SD) was evaluated as ‘response’ time in treatment groups. Response rates in DFMO, UFT, and DFMO plus UFT groups were 36.4%, 32.6% and 36.8%, respectively. DFMO demonstrated about the same level of tumor growth reduction as did UFT. No synergic effect was obtained by combined treatment. The animal model of the present study using tumor doubling time may provide a valuable test for new chemotherapeutic agents.

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