Chemotherapeutic, carcinogenic, and cell-regulatory effects of triazenes.

The following mouse strains were used: C57BL/6 x DBA2 F1 (hereafter called BD2F1), 6 to 10 weeks old (A. R. Schmidt Co., Madison, Wis.), AKR/J, and C57BL/6J (The Jackson Laboratory, Bar Harbor, Maine). All groups con sisted of 5 or 10 male mice. The mouse neoplasms studied were the parental line L1210 and sublines ofLl2lO resistant to methotrexate and 6-methylmercaptopurineriboside; L5178Y and its cytosine arabinoside-resistant subline L5178Y/CA55; and mast cell neoplasm P815 and its cytosine arabinoside-resistant subline. The antitumor effect of the 3 triazenes was studied with L1210. One million cells were implanted i.p. Treatment was started I day later and administered either i.p., s.c., or p.o., as a single injection or in 6 injections, 1 per day. The single dose of each drug used was lethal to 10% of the animals. These doses were determined by plotting dose-mortality data, which were obtained in normal male BD2F1 mice, on probability paper. The doses for 6 daily treatments caused less than 50% mortality in normal mice; a doubling of the doses caused death in most ofthe mice. DIC was suspended in 0.5% carboxymethylcellulose in dark bottles shortly before use. PDT and PMT were each dissolved in sesame oil and stored frozen at about —20°. DIC was supplied by the Drug Development Branch, Drug Research and Develop ment, Chemotherapy, National Cancer Institute, Bethesda, Md. PDT was obtained from Merck and Co., Rahway, N. J. PMT was synthesized by us (8). To induce tumors, 1 dose of PMT, 45 mg/kg, dissolved in