Document Detail


Monochloramine inhibits etoposide-induced apoptosis with an increase in DNA aberration.
MedLine Citation:
PMID:  11295536     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Monochloramine (NH(2)Cl) is a physiological oxidant produced by activated neutrophils, and it affects apoptosis signaling. We studied the effects of NH(2)Cl on the cell death induced by etoposide, a widely used anticancer agent that is directed to DNA topoisomerase II. Jurkat T cells, a human acute T cell leukemia cell line, were pretreated with 70 microM of NH(2)Cl for 10 min. After 24 h, 5-30 microM of etoposide was added to the NH(2)Cl pretreated and control cells, and their apoptosis, caspase activity, cell morphology, and cellular DNA contents were measured. NH(2)Cl pretreatment significantly inhibited apoptosis and caspase activation induced by etoposide or camptothecin, a DNA topoisomerase I poison, but not by staurosporine or Fas stimulation. The apoptosis inhibition actually resulted in the proliferation of the survived cells and, notably, the survived cells showed more aberrant morphology, such as variation in nuclear size, nuclear fragments, and multinucleated cells. DNA content analysis of the survived cells showed an increase in aneuploid nuclei. Cell cycle analysis after 24 h of NH(2)Cl treatment showed a significant decrease in S phase cells with a concurrent increase in G(0)/G(1) phase cells, which suggested that NH(2)Cl induced G(1) arrest. Using synchronized Jurkat cells, etoposide and camptothecin were found to be particularly cytotoxic to S phase cells, whereas staurosporine and Fas stimulation were not. Thus NH(2)Cl-induced G(1) arrest was a likely cause of the observed resistance to etoposide. These observations suggested that inflammation-derived oxidants may make the tumor cells more resistant to etoposide and increase the risk of tumor progression and the development of secondary tumors by increasing the survival of DNA damage-bearing cells.
Authors:
T A Than; T Ogino; M Omori; S Okada
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Free radical biology & medicine     Volume:  30     ISSN:  0891-5849     ISO Abbreviation:  Free Radic. Biol. Med.     Publication Date:  2001 Apr 
Date Detail:
Created Date:  2001-04-11     Completed Date:  2001-08-16     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  8709159     Medline TA:  Free Radic Biol Med     Country:  United States    
Other Details:
Languages:  eng     Pagination:  932-40     Citation Subset:  IM    
Affiliation:
Department of Pathology, Okayama University Medical School, Faculty of Medicine, Okayama, Japan.
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MeSH Terms
Descriptor/Qualifier:
Aneuploidy
Antibodies, Monoclonal / pharmacology
Antineoplastic Agents, Phytogenic / antagonists & inhibitors,  pharmacology
Apoptosis / drug effects*
Camptothecin / antagonists & inhibitors,  pharmacology
Caspases / metabolism
Cell Cycle / drug effects
Cell Division / drug effects
Cell Size / drug effects
Cell Survival / drug effects
Chloramines / pharmacology*
DNA / analysis
DNA Damage / drug effects*,  genetics
Enzyme Activation / drug effects
Etoposide / antagonists & inhibitors*,  pharmacology
Humans
Jurkat Cells
Oxidants / pharmacology*
Staurosporine / pharmacology
Chemical
Reg. No./Substance:
0/Antibodies, Monoclonal; 0/Antineoplastic Agents, Phytogenic; 0/Chloramines; 0/Oxidants; 0/anti-Fas monoclonal antibody; 10599-90-3/chloramine; 33419-42-0/Etoposide; 62996-74-1/Staurosporine; 7689-03-4/Camptothecin; 9007-49-2/DNA; EC 3.4.22.-/Caspases

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


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