Document Detail


Misonidazole hypoxic cytotoxicity and chemosensitization in two cell lines with different intracellular glutathione levels.
MedLine Citation:
PMID:  2138473     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Nitroimidazoles such as misonidazole (Miso) or SR-2508 are known to be cytotoxic to hypoxic cells and, with preincubation under hypoxic conditions, to sensitize cells to certain chemotherapy drugs, notably melphalan. In addition, these nitroimidazoles afford hypoxic radiosensitization; however, high intracellular glutathione (GSH) levels have been shown to significantly reduce radiosensitization by some nitroimidazoles. Using two cell lines that have an 8-fold difference in cellular GSH content, we have investigated whether inherent GSH levels influence Miso-induced hypoxic cytotoxicity, hypoxic GSH depletion, or chemosensitization to melphalan. Hypoxic incubation with varying concentrations of Miso resulted in greater cytotoxicity in Chinese hamster V79 cells than in A549 human lung adenocarcinoma cells, which have much higher GSH levels. However, the rate of GSH depletion for three concentrations of Miso was the same in the two cell lines, despite the large difference in inherent GSH levels. While the inherent sensitivity to melphalan was markedly different between the cell lines, hypoxic preincubation with 2 mM Miso with subsequent aerobic exposure to melphalan resulted in similar levels of sensitization. These results indicate that the potentiation of melphalan cytotoxicity by hypoxic Miso preincubation can occur independent of intracellular GSH levels.
Authors:
W G DeGraff; A Russo; N Friedman; J B Mitchell
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  European journal of cancer (Oxford, England : 1990)     Volume:  26     ISSN:  0959-8049     ISO Abbreviation:  Eur. J. Cancer     Publication Date:  1990 Jan 
Date Detail:
Created Date:  1990-05-07     Completed Date:  1990-05-07     Revised Date:  2005-11-17    
Medline Journal Info:
Nlm Unique ID:  9005373     Medline TA:  Eur J Cancer     Country:  ENGLAND    
Other Details:
Languages:  eng     Pagination:  17-20     Citation Subset:  IM    
Affiliation:
Radiation Biology Section, National Cancer Institute, Bethesda, MD 20892.
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MeSH Terms
Descriptor/Qualifier:
Animals
Cell Line
Cricetinae
Cricetulus
Drug Screening Assays, Antitumor
Glutathione / analysis*
Humans
Melphalan / pharmacology
Misonidazole / pharmacology*
Oxygen / physiology
Tumor Cells, Cultured / analysis,  drug effects*
Chemical
Reg. No./Substance:
13551-87-6/Misonidazole; 148-82-3/Melphalan; 70-18-8/Glutathione; 7782-44-7/Oxygen

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


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