The Stathmokinetic Effect of Vincristine

A single dose of vincristine produced an increase in the mitotic index in the marrow, duodenum, and hair follicle of the rat and in the marrow, hair root, and malignant tumors of man. This increase in mitotic index resulted from “arrest” of cells in metaphase; other stages of mitosis were not increased, and post-metaphase stages decreased during vincristine effect. This mitotic “arrest” may be associated with cell death as evidenced by a quantitative decrease in cellularity of the rat bone marrow following administration of vincristine. For all the above tissues the increase in mitotic index was linear for at least the first 6 hours after vincristine and reached a peak at approximately 12 hours. There was an inverse correlation between the magnitude of the mitotic index increase and the generation time for the various tissues. This mitotic effect does not relate regularly to the toxic effect. For example, vincristine and vinblastine produced comparable marrow mitotic “arrest” in man, whereas leukopenia occurred regularly only with vinblastine. The interrelationships and implications of these findings are discussed.