Antitumor Effect of 3-[(4-Amino-2-Methyl-5-Pyrimidinyl) Methyl]-1-(2-Chloroethyl)-1-Nitrosourea (ACNU) on Human Colon Carcinomas Transplanted into Nude Mice

Two human colon carcinomas serially transplanted into nude mice were used for experimental chemotherapy by 3-[(4-amino-2-methyl-5-pyrimidinyl)methyl]-1-(2-chloroethyl)-1-nitrosourea (ACNU). Human colon carcinomas Co-3 (well-differentiated adenocarcinoma) and Co-4 (poorly differentiated adenocarcinoma), were transplanted subcutaneously into the backs of BALB/c male nude mice. Tumor size was measured three times a week, and treatment was started when the estimated tumor weight reached 100 to 300 mg. Twenty and 40 mg of ACNU per kg was administered intravenously, once, dissolved in 0.2 ml of normal saline. There were marked tumor regression and histological tumor cell destruction in Co-4, whereas no effect was observed in Co-3. Microangiography revealed a similar vascular network in Co-3 and Co-4. Whole-body autoradiography was performed 5, 30, 180 and 360 minutes after 20 mg (286 μC1) of [ethylene-2-14C]-ACNU per kg was injected. ACNU concentration in the Co-3 tumor reached a peak 30 minutes after injection and diminished promptly with the decrease of ACNU in the blood, whereas in Co-4 tumors ACNU was retained in the tumor until 360 minutes after ad ministration. The effect of ACNU was thought to be correlated with the concentration of the drug in the tumor.