Nucleolar changes and fibrillarin redistribution following Apatone treatment of human bladder carcinoma cells

James M. Jamison, Jacques Gilloteaux, Laszlo Perlaky, Marc Thiry, Karel Smetana, Deborah Neal, Karen McGuire, Jack L Summers

Research output: Contribution to journalArticle


Ascorbate and menadione (Apatone) in a ratio of 100:1 kills tumor cells by autoschizis. In this study, vitamin-induced changes in nucleolar structure were evaluated as markers of autoschizis. Human bladder carcinoma (T24) cells were overlain with vitamins or with culture medium. Supernatants were removed at 1-hr intervals from 1 to 4 hr, and the cells were washed with PBS and prepared for assay. Apatone produced marked alterations in nucleolar structure including redistribution of nucleolar components, formation of ring-shaped nucleoli, condensation and increase of the proportion of perinucleolar chromatin, and the enlargement of nucleolar fibrillar centers. Immunogold labeling of the nucleolar rRNA revealed a granular localization in treated and sham-treated cells, and immunogold labeling of the rDNA revealed a shift from the fibrillar centers to the condensed perinucleolar chromatin. Fibrillarin staining shifted from the fibrillar centers and adjacent regions to a more homogeneous staining of the entire nucleolus and was consistent with the percentage of autoschizic cells detected by flow cytometry. Because autoschizis entails sequential reactivation of DNase I and DNase II, and because the fibrillarin redistribution following DNase I and Apatone treatment is identical, it appears that the nucleolar and fibrillarin changes are markers of autoschizis.

Original languageEnglish
Pages (from-to)635-651
Number of pages17
JournalJournal of Histochemistry and Cytochemistry
Issue number7
Publication statusPublished - Jul 2010
Externally publishedYes


  • Autoschizis
  • Carcinoma cells
  • Cell death
  • Fibrillarin
  • Immunogold
  • Nucleolus

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