Ultrastructural study of the effect of bleomycin A2 on the nucleolus and its possibly related cytoplasmic constituents in Novikoff hepatoma cells.

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 mug/ml in vitro produced an increased number of fibrillar centers with well-defined nucleolonemas. At a concentration of 50 mug/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 mug/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 mug/ml.