The Effect of Colchicine and X-ray on a Transplantable Mammary Carcinoma in Mice *

The first observations that the alkaloid colchicine affected the growth of neoplastic tissue were made by Dominici.7 He stated that patients with gout and cancer who were receiving colchicine showed a remarkable improvement in health. Amoroso' also noted similar beneficial effects in gouty patients with cancer. He reported complete retrogression of grafted tumors in mice which had received repeated small doses of colchicine subcutaneously. Dixon and Malden' observed marked leukocytosis in rabbits after administration of colchicine, and Dixon5 in his Manual of Pharmacology stated that colchicine was a substance that excited mitosis. Lits"2 and Dustin8' ' studied its effect on transplantable mouse tumors and observed a marked increase in mitotic figures, followed subsequently by pyknosis and necrosis of many of the dividing cells. They concluded that colchicine has a double action; first, it explosively stimulates mitotic division in all cells having the potentialities of division and, secondly, it arrests these dividing cells at the metaphase for a period of several hours and in large doses actually destroys them. They consider its action similar to that of several other substances previously studied by them which they call "caryoclastic poisons." Ludford"4 concluded that colchicine prevented the formation and proper function of the mitotic spindle. Thus, cells starting to divide while under the influence of colchicine are unable to complete their division and are arrested at the metaphase. The result is an accumulation of cells at the metaphase during the period of blockade, and this accounts for the apparent increase in mitotic activity. The studies of Brues2 on the effect of colchicine on regenerating liver in rats tend to support the observations of Ludford."4 Oughterson, Tennant, and Hirshfeld"5 observed a typical colchicine effect with a marked increase in the number of mitoses in a variety of human tumors after subcutaneous injection of from 2 to 5 mg. of the alkaloid. Attempts to produce regression of transplantable and spontane-