Effect of Urethane on Mouse Myelogeno us Leukemia

Abstract

The effects of urethane on normal and leukemic myeloid tissues of mice were investigated. The leukemia used was a transplanted myelogenous chloroleukemia in the 5th transfer generation. Chronic leukemia developed with the white blood count above 100,000 cells/c.mm. The disease developed in 76 of 77 inoculated mice and the blood picture was typical of myelogenous leukemia. Urethane was given intraperit., the daily dose being 0.004-1.0 mg./g. body wt. in 0.01 ml. of distilled water. After 3 daily doses, the white count dropped to normal, and the spleen and lymph nodes were reduced in size. Mature leucocytes appeared in the bone marrow. The effects were more profound than those noted after roentgen therapy. When the daily dose was dropped from 0.5 or 1.0 mg./g. to 0.2 mg./g., white counts dropped but wt. loss was not appreciable, and the lymph nodes and spleen were not reduced in size. Doses of less than 0.1 mg./g. did not alter the white counts. Two cases of spontaneous mouse leukemia were also treated with urethane. One, a lymphatic leukemia with a white count of 63,000, failed to respond to 0.2 mg./g. daily. The second, a myelogenous leukemia, exhibited a fall in leucocyte count from 82,000-20,000 in 1 wk. as well as a decrease in the size of the spleen. Urethane depressed the white count of nonleukemic human subjects. Doses of 0.5 or 1.0 mg./g. in normal mice produced a similar effect, but neither the drop in leucocyte count nor loss of body wt. was as rapid as in leukemic mice similarly treated. Daily doses of 0.2 mg. or less/g. given for 3 wks. were nontoxic for normal mice. Doses which affected leukemic marrows caused no marked cellular changes in the bone marrow of normal mice.