The antitumoral activity of 4'-deoxydoxorubicin compared to doxorubicin and 5-fluorouracil on methylazoxymethanol acetate-induced colon tumors in CF1 mice

Abstract

The suitability of carcinogen-induced colon tumors in mice for chemotherapy investigations and the potential antitumoral activity of a new anthracycline, 4'-deoxydoxorubicin (4' deoDX ) were evaluated. The latter was compared with 5-fluorouracil (5-FU) and doxorubicin (DX) either alone or in combination. CF1 mice were given 10 weekly subcutaneous injections of methylazoxymethyl acetate (MAM) and killed between 16 and 39 weeks after delivery of the first carcinogen treatment. The number and size of macroscopic tumors was observed; only 6% of mice showed no tumor development (19 of 327). Statistically significant reduction of tumor size occurred at a tolerated dose of 5-FU given as six intravenous injections (46 mg/kg) (P less than 0.05). With 4' deoDX a significant decrease in tumor number was observed using four weekly injections of 2.7 mg/kg (P less than 0.05) or six weekly injections of 5 mg/kg (P less than 0.05). Given in combination, 4' deoDX (3.3 mg/kg) and 5-FU (23 mg/kg) demonstrated a statistically significant reduction of the tumor number as compared with the untreated controls (P less than 0.025). Moreover, this reduction was greater than the observed response with any dose levels of the single compound thus demonstrating a potentiation of activity. These results indicate that MAM-induced colonic tumors are an appropriate model for the assessment of chemotherapeutic drugs. Moreover, 4' deoDX showed antitumoral activity comparable with 5-FU indicating this new anthracycline may be a useful candidate either alone or combined with 5-FU for clinical trials against colon cancer.