THE EFFECT OF URETHANE ON THE NUCLEAR MORPHOLOGY OF CELLS OF THE GRANULOCYTE SERIES AS OBSERVED IN MARROW CULTURES AND LEUKEMIC BLOOD

In cultures by the marrow culture technic of human marrow and leukemic blood containing concentrations of urethane from 1:200 to 1:40,000, marked changes in the morphology of the cells of the granulocyte series were noted. These changes were not noted in the control nor in duplicate cultures containing the methyl-bis (B-chloroethyl) amine hydrochloride form of nitrogen mustard in concentrations from 1:500,000 to 1:40,000,000, nor were they noted in previous studies of cultures containing colchicine or exposed to 200 kilovolt or million volt x-rays, neutron rays or radioactive phosphorus, nor in the bloods or marrows of patients with untreated chronic granulocytic leukemia, of healthy individuals or of persons with miscellaneous diseases. The changes consisted of an early increase in number of normal mitoses in the progranulocytes; a steadily rising percentage of granulocytes and progranulocytes showing condensation of the chromatin in the nucleus into dense fragments separated by clear spaces; a progressive increase in the number of cells of the granulocyte series with double nuclei, affecting all cells from the progranulocytes to the neutrophil lobocytes but appearing to be most numerous in the granulocyte stage; and the appearance in the cultures by 4 to 5 days of cells containing separated fragments of structureless material staining like basichromatin, which probably represents a karyorrhexis of the nucleus. Note: Nothing in this article is to be construed as a recommendation of urethane for the clinical treatment of leukemias. While many years must elapse before its place in therapy can be evaluated, it does seem worthwhile to give urethane a trial for metastatic malignant tumors. Our present impression is that either radioactive phosphorus or total body irradiation with x-rays given in small regularly spaced doses is far superior to urethane in the treatment of leukemias.17 When the cells become resistant to radiation therapy, urethane may be worthy of a trial.