Document Detail

Iodine-131 induces mitotic catastrophes and activates apoptotic pathways in HeLa Hep2 cells.
MedLine Citation:
PMID:  18986216     Owner:  NLM     Status:  MEDLINE    
Iodine-131 (131I) has been used both in unconjugated form and conjugated to antibody derivates (i.e., radioimmunotherapy; RIT) to treat malignant diseases. The mechanisms by which 131I-irradiation causes growth retardation are, however, inadequately understood. The aim of this study was to elucidate the sequential molecular and cellular events that initiate cell death in HeLa Hep2 cells exposed to 131I. In this paper, HeLa Hep2 cells were found to display a transient G2-M arrest following irradiation, but then reentered the cell cycle still containing unrepaired cellular damage. An increase of multipolar mitotic spindles, as well as a significant increase in centrosome numbers from 8.8% +/- 1.9% in controls to 54.7% +/- 2.2% in irradiated cells, was observed (p < 0.0001). A subsequent failure of cytokinesis caused the cells to progress into mitotic catastrophe. This was accompanied by the formation of giant cells with multiple nuclei, multilobulated nuclei, and an increased frequency of polyploidy cells. A fraction of the cells also displayed apoptotic features, including the activation of initiator caspases-2, -8, -9, and effector caspase-3, as well as cleavage of poly(ADP-ribose) polymerase, a cell-death substrate for active caspase-3. These findings demonstrate that mitotic catastrophes and the activation of a delayed type of apoptosis might be important mechanisms involved in cell death following the RIT of solid tumors with -emitting radionuclides, such as 131I.
David Eriksson; Jeanette Blomberg; Theres Lindgren; Per-Olov Löfroth; Lennart Johansson; Katrine Riklund; Torgny Stigbrand
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Cancer biotherapy & radiopharmaceuticals     Volume:  23     ISSN:  1557-8852     ISO Abbreviation:  Cancer Biother. Radiopharm.     Publication Date:  2008 Oct 
Date Detail:
Created Date:  2008-11-14     Completed Date:  2009-02-04     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9605408     Medline TA:  Cancer Biother Radiopharm     Country:  United States    
Other Details:
Languages:  eng     Pagination:  541-9     Citation Subset:  IM    
Department of Immunology, Umeå University, Umeå, Sweden.
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MeSH Terms
Caspases / metabolism
Cell Line
Cell Nucleus / metabolism
Centrosome / radiation effects
Enzyme Activation
Flow Cytometry / methods
Hela Cells
Iodine Radioisotopes / pharmacology*
Microscopy, Fluorescence / methods
Neoplasms / radiotherapy*
Poly(ADP-ribose) Polymerases / metabolism
Radioimmunotherapy / methods
Reg. No./Substance:
0/Iodine Radioisotopes; EC Polymerases; EC 3.4.22.-/Caspases

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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