[THERAPEUTIC EFFECT OF AT-581 ON THE BROWN-PEARCE CARCINOMA IN RABBITS AND ITS INFLUENCE ON MITOSIS OF THE TUMOR CELLS].

o-[Bis-(2-chloroethyl)-aminomethyl]-phenylalanine dihydrochloride, designed as AT- 581, is a new derivative of nitrogen mustard.In this paper we have studied further the therapeutic effect of the drug on the Brown-Pearce carcinoma and its influence on mitosis of the carcinoma cells. 1.In rabbits, the Brown-Pearce carcinoma was transplanted into the anterior cham- bers of the eye by using the suspension or tumour piece inoculation method, and the treatment with AT-581 was started on the 3rd day after the inoculation.It was found that intravenous injections of 0.7 mg/kg could markedly inhibit the tumour growth, the degree of inhibition being about 48-78%. When the drug was injected intraocularly at the dosages of 0.015, 0.03 and 0.06 mg/eye, the therapeutic effect was also significant. 2. When AT-581 was injected intravenously for 3 or 7 days to rabbits bearing the Brown-Pearce carcinoma, the mitotic index (counting 3000 cells) was decreased signifi- cantly and the percentages of all four stages of mitosis were depressed, among them the metaphase being affected most strikingly. Other morphologic changes such as disarrange- ment and pyknosis of the tumour cells, coagulation and fragmentation of the nuclei, and necrosis of the tumour tissue were also noticed. 3.A single intravenous injection of a small dose of AT-581 produced firstly a stimulating action on the growth of tumour cells, and then a remarkable inhibitory effect. Larger doses of the drug caused immediate mitotic inhibition including a decrease of mitosis in all four stages, and a pyknosis of the tumour cells.