The Effect of Repeated Doses of Urethane (Ethyl Carbamate) on the Mitotic Activity and Cellular Composition of the Bone Marrow of Normal Mice

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Abstract
A single dose of urethane produced a rise in the mitotic index, due essentially to a large increase in the metaphase index in the bone marrow of normal mice. Repeated daily injections (three and six doses) produced an elevation of the mitotic index, which was, however, smaller than that observed after a single dose of urethane. After nine doses of urethane the mitotic index was found approximately at the same level as in the controls. The mitotic index in the bone marrow of urethane-treated mice never decreased below the normal level found in untreated mice. After three, six and nine doses of urethane a rise in the percentage of ana- and telophases was found, in contrast to the increase in the percentage of metaphases after administration of a single dose of urethane. The percentage of prophases was decreased after six and nine doses of urethane. The morphological changes in the mitotic figures were the same as those described after a single dose of urethane. They consisted mainly in bridge formation and chromosome aberrations in anaphase. Very large promyelocytes, often with prematurely lobated or bizarre shaped nuclei, were observed. There was damage to the nuclei of the erythroid precursors and consequently an increase in the myeloid-erythroid ratio in the bone marrow after repeated doses of urethane, especially after nine doses. The maturation rate of the segmented leukocytes in the bone marrow of the urethane treated mice was augmented after repeated doses.