Comparison of antitumor activities of nitrosourea derivatives against mammary breast carcinoma (MX-1) in nude mice.

Abstract

A study was conducted to evaluate the antitumor activities of six nitrosourea derivatives against the xenograft of mammary breast carcinoma transplanted in nude mice (MX-1). The drugs employed in this study were 3-[(4-amino-2-methyl-5-pyrimidinyl)methyl]-1-(2-chloroethyl)-1-nitrosourea hydrochloride (ACNU), 1-(2-chloroethyl)-3-(methyl alpha-D-glucopyranos-6-yl)-1-nitrosourea (MCNU), 1-(2-chloroethyl)-3-(beta-D-glucopyranosyl)-1-nitrosourea (GANU), 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU), 1-(2-chloroethyl)-3-(4-methylcyclohexyl)-1-nitrosourea (Me-CCNU), and 2-[3-(2-chloroethyl)-3-nitrosoureido]-2-deoxyl-D-glucopyranose (DCNU, chlorozotocin). CCNU and Me-CCNU were administered intraperitoneally, and the other were given intravenously through a tail vein. Antitumor activities were assessed in terms of the drug-induced tumor growth inhibition based on caliper measurements. A single treatment with ACNU (40 mg/kg) induced 92% tumor regression, compared to 73% and 69% tumor regression induced by MCNU (15 mg/kg) and CCNU (50 mg/kg), respectively. GANU and DCNU were less effective. To evaluate the antitumor activity of the drugs, we employed the predetermined dose lethal to one-tenth of BDF1 mice (LD10) for each drug as a standard therapeutic dose to nude mice; doses higher than LD10 and one-half and/or one-fourth of LD10 were also given. The results suggest that LD10 in BDF1 mice could be employed as a standard therapeutic dose in the chemotherapy of nude mice.