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Comparative Ultrastructural Studies of Nucleoli of Tumor Cells Treated with Adriamycin and the Newer Anthracyclines, Carminomycin and Marcellomycin¹

Department of Pharmacology, Baylor College of Medicine, Houston, Texas 77030

This study was designed to determine the effects of several antitumor anthracyclines, including Adriamycin and its analogs, carminomycin and marcellomycin, on the ultrastructure of nucleoli of Novikoff hepatoma cells.

Adriamycin and carminomycin, which are structurally related, induce nucleolar segregation following the formation of conspicuous fibrillar centers. Marcellomycin did not induce formation of nucleolar fibrillar centers. Instead, numerous microspherules formed following treatment with marcellomycin; later complete nucleolar segregation developed.

The microspherules were observed to be in various stages of extrusion from the nucleolar body. This microspherule "migration" appeared to be both time and drug concentration dependent. These results show that the rate and extent of nucleolar ultrastructural aberration may be related to structural differences of the various anthracyclines.

¹ These studies were supported by Cancer Research Center Grant CA-10893, P5, awarded by the National Cancer Institute, Department of Health, Education, and Welfare, a grant from the Bristol Laboratories, the Pauline Sterne Wolff Memorial Foundation, a gift from Dr. and Mrs. O. A. Breiling, and a generous gift from Mrs. Jack Hutchins.

Received 8/ 1/77. Accepted 11/11/77.