The Cytological Effect of Chemicals on Ascites Sarcomas IV. A phase microscopy study of the damage to the tumor cells by podophyllin1)

It has been well shown through the observations both in vivo (King and Sullivan 1947, Belkin 1948, Greenspan, Leiter and Shear 1950, Leiter, Downing, Hartwell and Shear 1950, MacCardle 1951, Makino and Tanaka 1953, etc.) and in vitro (Ormsbee, Cornman and Berger 1949, Makino and Cornman 1953) that podophyllin and its components do exert a powerful mitotic poisoning effect and do damage both malignant cells and normal tissues. The mechanism of their destructive effects as mitotic poisons, however, has remained unexplored. Ormsbee, Cornman and Berger (1949) suggested that podophyllin contains not only mitotic poisons but also some other substance or substances which selectively damage tumor cells by a mechanism other than that of disrupting cell division. Cornman and Cornman (1951) are of opinion that the destructive effects of podophyllin appear to exceed that which is explainable solely as a result of mitotic effects. Previous observations of damage by podophyllin and its derivatives to rat ascites tumors in vivo (Makino and Tanaka 1953, Tanaka et al. 1955) have shown that these chemicals extensively attack mitosis. In podophyllin treated animals, the division of tumor cells is arrested at metaphase, the chromosomes agglutinate into several clumps, and nuclear disintegration follows (Tanaka and Makino 1953). To obtain supplementary data upon the role of mitotic effects of podophyllin, the changes of living tumor cells in response to exposure to podophyllin have been followed in this, study by phase micro scopy using the temporary hanging-drop preparation. The authors are grateful to Mr. H. Nakahara for his kind help in securing the data for this paper. They are also indebted to Dr. I. Cornman of the George Washington University Cancer Clinic, Washington, D. C., U. S. A. for his kindness in supplying the drug used for this experiment.