CANCER CHEMOTHERAPY MODEL USING AUTOCHTHONOUS LARGE BOWEL CANCER IN RATS

Abstract

Chemotherapy of methylnitrosourea-induced autochthonous large bowel cancer in rats, which is similar to that in man, was studied to evaluate the intrarectal [ir] administration or topical application of chemotherapeutic agents. Rats with large bowel tumors confirmed by endoscopic examination received an ir 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 group), i.p. injection of 2.5 mg of 5-fluourouracil (i.p. group) daily for 8 wk. All rats, including nontreated control rats, were necropsied after treatment. The number of large bowel tumors per rat detected by endoscopy before treatment was the same among groups, whereas that observed at necropsy after treatment was significantly smaller in the ir group, compared to nontreated and i.p. groups. The tumors increased significantly in rats of nontreated and i.p. groups between endoscopy and necropsy, but not in rats of the ir groups. The maximum tolerated dosage of the agents administered ir suppressed the development of new tumors after the start of treatment and also the growth of tumors detected by endoscopy before treatment.