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Ultrastructural Study of the Effect of Bleomycin A₂ on the Nucleolus and Its Possibly Related Cytoplasmic Constituents in Novikoff Hepatoma Cells¹

The Electron Microscopy Unit, Tumor By-Products Laboratory, Department of Pharmacology, Baylor College of Medicine, Houston, Texas 77025

Treatment of Novikoff hepatoma ascites cells with bleomycin A₂, in vivo as well as in vitro, in varying doses produced marked alterations in nucleolar and cytoplasmic ultrastructural organization. A series of changes occur including formation of fibrillar centers, fragmentation of fibrillar nucleolar elements, appearance of microspherules, and the loss of fibrillar elements from these nucleoli.

A bleomycin concentration of 10 µg/ml in vitro produced an increased number of fibrillar centers with well-defined nucleolonemas. At a concentration of 50 µg/ml, there was an increase in number and fragmentation of these fibrillar centers and many microspherules were found throughout the nucleolus. Approximately one-fourth of the cells contained cytoplasmic fibrillar bodies and amorphous fibrous tufts around the nuclear envelope. At a bleomycin concentration of 100 µg/ml, the nucleoli contained more granular elements and numerous microspherules. Almost 90% of the cells contained cytoplasmic fibrillar bodies. The effects of bleomycin in vivo (10 mg/kg) closely resemble those found in vitro with concentrations of 50 and 100 µg/ml.

¹ These studies were supported in part by USPHS Grant CA-10893 and a gift by Mrs. Jack C. Hutchins.

Received 7/26/74. Accepted 10/11/74.