Morphology and DNA degeneration during autoschizic cell death in bladder carcinoma T24 cells induced by ascorbate and menadione treatment

Anat Rec A Discov Mol Cell Evol Biol. 2006 Jan;288(1):58-83. doi: 10.1002/ar.a.20276.


Feulgen and actin-phalloidin staining as well as gel electrophoresis have been employed in conjunction with cell ultrastructure to describe the effects of 1-, 2-, and 4-hr ascorbate (VC), menadione (VK(3)), and ascorbate:menadione (VC:VK(3)) treatments on the T24 human bladder carcinoma cell line. T24 cells exposed to VC alone display blebs and other superficial membrane defects related to membrane alterations and to superficial cytoskeleton changes. VK(3) treatment damages the cell nucleus and organelles, leads to the redistribution of the organelles in the perikaryon as a consequence of cytoskeletal damage, and results in cytoplasmic self-excisions. After VC:VK(3) treatment, the cells show exaggerated alterations characteristic of each vitamin treatment alone, including damaged mitochondria, self-excision of organelle-free pieces of cytoplasm, and extrusion of the perikaryon containing a nucleus surrounded by the damaged organelles. The nuclear envelope appears intact and contains chromatin that decondenses and dissipates. During the cellular demise that concludes with apparent karyolysis, the cells significantly decrease their size and alter their shape. However, the cisterns of rough endoplasmic reticulum are undamaged, but may become dilated. Since the cellular phenomena leading to cell death differ morphologically from apoptosis and necrosis, but entail self-cutting without nuclear bodies, this new form of cell death was called autoschizis. In addition, gel electrophoresis and Feulgen staining demonstrate that autoschizis is accompanied by random DNA degeneration.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Ascorbic Acid / pharmacology
  • Carcinoma / pathology
  • Cell Death / drug effects
  • Cell Death / physiology*
  • Cell Line, Tumor / drug effects
  • Cell Line, Tumor / ultrastructure*
  • DNA Fragmentation
  • Densitometry
  • Drug Synergism
  • Electrophoresis
  • Histocytochemistry
  • Humans
  • Rosaniline Dyes
  • Urinary Bladder Neoplasms / pathology
  • Vitamin K 3 / pharmacology


  • Feulgen stain
  • Rosaniline Dyes
  • Vitamin K 3
  • Ascorbic Acid