Document Detail


Effects of N-methylformamide on the growth, cell cycle, and glutathione status of murine TLX5 lymphoma cells.
MedLine Citation:
PMID:  3370637     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The growth of the murine TLX5 lymphoma is inhibited in vivo by administration of N-methylformamide (Gescher, A., et al., Br. J. Cancer, 45: 843-850, 1982). Continuous incubation of TLX5 murine lymphoma cells in vitro with N-methylformamide for 72 h, at concentrations of between 43 and 170 mM (0.25 and 1% v/v), brought about a concentration-dependent decrease in growth rate (50% inhibitory concentration = 68 mM) and viability. Cell replication was decreased by 37% after 48 h exposure to 106 mM N-methylformamide, while viability was maintained at 82%. Analysis of the distribution of these cells in the cell cycle by flow cytofluorimetry showed a 23% increase in the proportion of G1 cells and a fall in the proportion of cells in the S and G2/M phases. As the drug concentration and time of exposure to N-methylformamide were increased, with an associated reduction in cell replication and viability, the proportion of G1 cells rose. When TLX5 cells were washed free of N-methylformamide after an exposure to 106 mM for 48 h and cultured in drug-free medium, the cells returned to exponential growth and to a normal cell cycle distribution. Clonogenic assays showed that the recovery of proliferation, after removal of the drug, was due to that of all those cells which, in a parallel experiment, excluded the dye trypan blue. It is concluded that the cessation of replication and the accumulation of cells in G1 of the cell cycle, after treatment with N-methylformamide, are probably not events representative of terminal differentiation but rather of cytostasis, which was accompanied by rapid cell death. Coincident with the reduction of TLX5 cell proliferation caused by N-methylformamide and the accumulation of cells in G1, cellular glutathione concentrations fell by 80%. A similar fall was induced by treatment of the cells with D,L-buthionine[S,R]-sulfoximine (5 microM) for 48 h, but this treatment had no effect on cell growth.
Authors:
C A Bill; A Gescher; J A Hickman
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Cancer research     Volume:  48     ISSN:  0008-5472     ISO Abbreviation:  Cancer Res.     Publication Date:  1988 Jun 
Date Detail:
Created Date:  1988-06-29     Completed Date:  1988-06-29     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  2984705R     Medline TA:  Cancer Res     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  3389-93     Citation Subset:  IM    
Affiliation:
Pharmaceutical Sciences Institute, Aston University, Birmingham, United Kingdom.
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MeSH Terms
Descriptor/Qualifier:
Animals
Buthionine Sulfoximine
Cell Cycle / drug effects
Cell Survival / drug effects
Formamides / pharmacology*
Glutathione / metabolism*
Lymphoma / metabolism,  pathology*
Methionine Sulfoximine / analogs & derivatives,  pharmacology
Mice
Mice, Inbred CBA
Tumor Cells, Cultured
Chemical
Reg. No./Substance:
0/Formamides; 123-39-7/methylformamide; 1982-67-8/Methionine Sulfoximine; 5072-26-4/Buthionine Sulfoximine; 70-18-8/Glutathione

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