Toxicity of microtubular drugs to leukemic lymphocytes

The work was designed to test the hypothesis that the cytocidal action of vincristine and colchicine on nondividing leukemic lymphocytes is due to the action of the alkaloids on the microtubules of the cells. Lymphocytes from normal persons and from patients with chronic lymphocytic leukemia were incubated with microtubular reagents and viable lymphocyte counts were made by phase-contrast microscopy before and after incubation. Nondividing leukemic lymphocytes were found to be more sensitive than normal lymphocytes, not only to vincristine and colchicine, but also to vinblastine, podophyllotoxin, maytansine, oncodazole, and 2-methoxy(trimethoxyphenyl)tropone, all of which arrest mitotic cells in metaphase by combining with tubulin, the subunit of microtubular protein. Griseofulvin, which combines with microtubular associated proteins, was not toxic to leukemic lymphocytes. D 2O which stabilizes microtubules, protected leukemic lymphocytes from colchicine and podophyllotoxin, but not from vincristine. Lumicolchicine, an analog of colchicine, does not disrupt microtubules and was not toxic to leukemic lymphocytes. These findings are consistent with the proposed hypothesis.