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A water-soluble nitrosourea, 3-[(4-amino-2-methyl-5-pyrimidinyl)methyl]-1-(2-chloroethyl)-1-nitrosourea hydrochloride (ACNU), was tested for antitumor activity against lymphoid leukemia L-1210 in BDF1 mice. The results obtained were as follows: (1) ip--ip system: By daily administrations optimal dose for 12 days, MED (ILS40), and therapeutic ratio were found to be 18 mg/kg, 1.3 mg/kg, and 14, respectively, and by a single injection, those were found to be 46 mg/kg, 4.2 mg/kg, and 11, respectively. The therapeutic ratio of ACNU was the highest of all the drugs tested. At the neighboring dose level to optimal dose most of leukemic mice survived more than 60 days. (2) ip--iv system: Remarkable prolongation of life-span was observed by a single injection. Majority of mice administered more than 32 mg/kg of ACNU survived more than 60 days. (3) ip--po system: Remarkable prolongation of life-span was shown by a single administration and most of leukemic mice given more than 46 mg/kg of ACNU survived over 60 days. (4) iv--ip system: By a single administration of ACNU remarkable prolongation of life-span was seen and majority of leukemic mice were rescused at doses of 32 mg/kg or more. (5) iv--iv system: Result almost similar to iv--ip system was obtained. (6) iv--po system: The result in this system was similar to that in ip--po system. Thus, the compound was highly effective in leukemic mice by either its parenteral or oral administration.

Effect of 3-[4-amino-2-methyl-5-pyrimidinyl)ethyl[-1(2-chloroethyl)-1-nitrosourea hydrochloride on lymphoid leukemia L-1210.