Reduced growth rate of dimethylhydrazine-induced colon tumors in rats

Abstract

alpha-Difluoromethylornithine (DFMO) treatment has been shown to modify carcinogenesis in many experimental tumor models, including breast, urinary bladder, and colon. This study was designed to determine whether DFMO treatment can inhibit tumor growth on chemical-induced colon cancer in rats. Effectiveness of DFMO in combination with mitomycin C (MMC) was also evaluated. Forty-two Sprague-Dawley rats received dimethylhydrazine (20 mg/kg) s.c. once weekly for 20 wk to induce colon cancer. Then a double-contrast barium enema was performed, and colon tumors were detected. The animals were divided into four groups that were subjected to the following treatment: none; DFMO alone; MMC alone; and a combination of DFMO plus MMC. After 5 wk of treatment, the barium enema was repeated. For the evaluation of treatment efficacy, tumor doubling time was adopted. The mean tumor doubling time in the control group was 20.7 +/- 9.1 days (SD). "Response" was judged as effective when tumor doubling time in treatment groups was more than 38.9 days, calculated from the mean + 2 SDs in the control group. Response rates in the DFMO, MMC, and DFMO plus MMC groups were 40.0%, 10.0%, and 82.3%, respectively. DFMO was a more effective inhibitor of tumor growth than MMC, and DFMO in combination with MMC resulted in a synergic diminution of tumor growth. The double-contrast barium enema is useful to observe sequential tumor growth and may be appropriate for the evaluation of new treatment on experimental colon cancer in rats.