Document Detail


Cytological effects of 1-(2-nitro-1-imidazolyl)-3-methoxy-2-propanol (misonidazole) on hypoxic mammalian cells in vitro.
MedLine Citation:
PMID:  626969     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Hypoxic Chinese hamster V-79 cells were examined for light-microscope morphology, progression through the cell cycle, chromosomal aberrations, and viability, after incubation with the 2-nitroimidazole, misonidazole [1-(2-nitro-1-imidazolyl)-3 methoxy-2-propanol]. Cytological examination of cells up to 42 hr after incubation with the drug at 37 degrees indicated that increasing contact time and increasing drug concentrations interfered with cell attachment and progressively slowed cell progression through the cell cycle. Forty-two hr after a 5.5-hr treatment with 5 mM misonidazole, the majority of cells contained heteropyknotic nuclei, whereas less than 3% had progressed into mitosis. Of the few cells that reached mitosis by 42 hr, the level of chromosomal aberrations was 6 times that due to hypoxia alone. However, the majority of metaphases (70%) were unaltered; thus about 2% of the treated cell population passed into mitosis unaltered. After a 5.5-hr incubation with 5 mM misonidazole, 98% of the cells also had lost their ability to produce clones. It is suggested that the cytotoxic effect of this drug on hypoxic cells is that the cytotoxic effect of this drug on hypoxic cells is largely mediated via an interphase cell death, with a minor effect due to chromosome aberrations and cell death from genetic inequality of progeny cells. The ability of misonidazole to kill hypoxic, noncycline cells, which may limit the curability of some tumors with conventional X-rays or chemotherapy agents, makes it of considerable potential interest.
Authors:
C R Geard; S F Povlas; M B Astor; E J Hall
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, Non-P.H.S.; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Cancer research     Volume:  38     ISSN:  0008-5472     ISO Abbreviation:  Cancer Res.     Publication Date:  1978 Mar 
Date Detail:
Created Date:  1978-04-26     Completed Date:  1978-04-26     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  2984705R     Medline TA:  Cancer Res     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  644-9     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Anaerobiosis*
Cell Cycle / drug effects*
Cell Line
Cell Survival / drug effects*
Chromosome Aberrations*
Metabolism*
Mitosis / drug effects
Nitroimidazoles / pharmacology*
Time Factors
Chemical
Reg. No./Substance:
0/Nitroimidazoles

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


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