Document Detail

Paraquat-induced cytoskeletal injury in cultured cells.
MedLine Citation:
PMID:  3672519     Owner:  NLM     Status:  MEDLINE    
Although the redox cycling of paraquat (PQ) and the resultant "activated oxygen" generation are important in toxicity development, the intracellular events leading to cell injury remain unclear. To understand the mechanism of PQ-induced cell injury, we have studied the effects of PQ on DNA synthesis, cell proliferation, the cytoskeletal organization, particularly microtubules (MT) and microfilaments (MF), and the synthesis and composition of cytoskeletal proteins in mouse 3T3 cells. PQ treatment produced a dose-dependent inhibition of DNA synthesis and cell growth. Exposure of cells to PQ (313 microM, 20 hr) resulted in MT aggregation and bundling as well as MF redistribution in the perinuclear area as revealed by fluorescence microscopy. Although this PQ dose inhibited DNA synthesis by 95%, it caused only a 22% decrease in protein synthesis of the cytoskeletal fraction. Higher doses of PQ (1250 microM, 20 hr) caused (a) dramatic thinning out and loss of MT and (b) marked loss of MF cables and the appearance of numerous pine needle-like structures much finer and shorter than normal MF. Under these conditions, the synthesis of cytoskeletal proteins was decreased by about 83%. Further analysis of the cytoskeletal fraction from PQ-treated cells by sodium dodecyl sulfate gel electrophoresis showed (a) that tubulin was greatly diminished, in agreement with microscopic observations; (b) that two new protein bands appeared; and (c) another protein band which was also reduced considerably. These results indicate that the PQ-induced dose-dependent cytoskeletal injury may be important to the mechanism of cytotoxicity of this herbicide.
W D Li; Y Z Zhao; I N Chou
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Toxicology and applied pharmacology     Volume:  91     ISSN:  0041-008X     ISO Abbreviation:  Toxicol. Appl. Pharmacol.     Publication Date:  1987 Oct 
Date Detail:
Created Date:  1987-11-23     Completed Date:  1987-11-23     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0416575     Medline TA:  Toxicol Appl Pharmacol     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  96-106     Citation Subset:  IM    
Department of Microbiology, Boston University School of Medicine, Massachusetts 02118.
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MeSH Terms
Cell Line
Cytoskeletal Proteins / analysis,  biosynthesis
Cytoskeleton / drug effects*
DNA / biosynthesis,  drug effects
Dose-Response Relationship, Drug
Electrophoresis, Polyacrylamide Gel
Microfilaments / drug effects
Microscopy, Fluorescence
Microtubules / drug effects
Paraquat / toxicity*
Reg. No./Substance:
0/Cytoskeletal Proteins; 4685-14-7/Paraquat; 9007-49-2/DNA

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

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