The effect of urethane on the nuclear morphology of cells of the granulocyte series as observed in marrow cultures and leukemic blood.

I NTEREST in urethane (NH2’CO.OC2H5) and related carbamic acid esters in the treatment of metastatic malignant tumors and leukemias has been greatly stimulated by the report of Haddow and Sexto& on the effects of urethane on tumors in experimental animals, and of Paterson, Haddow, Thomas and Watkinson2 on urethane therapy of human leukemias and malignant tumors. They demonstrated striking decreases in the leukocyte count and spleen size in certain patients with granulocytic or lymphocytic leukemias and in the size of metastatic nodules in a small proportion of patients with other malignant tumors. The observations of Paterson, Haddow, Thomas and Watkinson2 have been confirmed by Goodman and Lewis3 and by the authors at the University of Oregon Medical School. Although urethane has long been in use as a narcotic and there is much literature On the action of the urethanes and related karyokiastic and karyokinetic poisons on the cells of lower forms of life,4 we were unable to find any reference to morphologic changes produced by urethane in the nuclei of human cells. The present study, using the technic of human marrow culture,5 was undertaken as part of a long-term investigation of the factors influencing the fundamental phases of cell growth, namely, increase in size, mitotic and amitotic division, differentiation, and life span. This paper will be limited to the morphologic changes in cells of the granulocyte series produced by the action of urethane. Quantitative data on the comparative effects of urethane and methyl-bis (B-chloroethyl) amine hydrochloride obtained in the course of this study will appear later.