Cancer chemotherapy model using autochthonous large bowel cancer in rats

Chemotherapy of methylnitrosourea-induced autochthonous large bowel cancer in rats, which is similar to that in man, was studied to evaluate the intrarectal administration or topical application of chemotherapeutic agents. Rats with large bowel tumors confirmed by endoscopic examination received an intrarectal instillation of 1 mg of 1-(4-amino-2-methyl-5-pyrimidinyl)methyl-3-(2-chloroethyl)-3-nitrosourea hydrochloride (ACNU), 1 mg of 1-(2-chloroethyl)-3-(4-methylcyclohexyl)-1-nitrosourea (Me-CCNU), or 5 mg of 5-fluorouracil (ir groups), or intraperitoneal injection of 2.5 mg of 5-fluorouracil (ip group) daily for 8 weeks. All the rats, including non-treated control rats, were necropsied after the treatment. The number of large bowel tumors per rat detected by endoscopy before the treatment was mostly the same among groups, whereas that observed at necropsy after the treatment was significantly smaller in ir groups, compared to non-treated group and ip group. The tumors increased significantly in rats of non-treated group and ip group between the time of endoscopy and necropsy, but not in rats of ir groups. These results showed that the maximum tolerated dosage of the agents administered intrarectally suppressed the development of new tumors after start of the treatment and also the growth of tumors which were detected by endoscopy before the treatment.