Document Detail

Acute exposure of human lung cells to 1,3-butadiene diepoxide results in G1 and G2 cell cycle arrest.
MedLine Citation:
PMID:  15688362     Owner:  NLM     Status:  MEDLINE    
1,3-Butadiene (BD) causes genetic damage, including adduct formation, sister chomatid exchange, and point mutations. Previous studies have focused on the types of genetic damage and tumors found after long-term exposure of rodents to butadiene. This study examined the effect of the most active BD metabolite, butadiene diepoxide (BDO2), on cell cycle entry and progression in human lung fibroblasts (LU cells) with a normal diploid karyotype. Serum-arrested (G0) LU cells were exposed to BDO2 for 1 hr and stimulated to divide with medium containing 10% fetal bovine serum. The BDO2-treated LU cells were evaluated for cell cycle progression, nuclear localization of arrest mediators, mitotic index, and cellular proliferation. The BDO2-treated cells demonstrated a substantial inhibition of cell proliferation when treated with 100 microM BDO2 for 1 hr. No appreciable levels of apoptosis or mitotic figures were observed in the BDO2-treated cells through 96 hr posttreatment. Flow cytometric analysis revealed that the lack of proliferation in BDO2-treated LU cells was related to G1 arrest in about half of the cells and a delayed progression through S and G2 arrest in nearly all of the remaining cells. Both G1 and G2 arrest were prolonged and only a very small percentage of BDO2-treated cells were eventually able to replicate. Increased nuclear localization of both p53 and p21(cip1) was observed in BDO2-treated cells, suggesting that the cell cycle arrest was p21(cip1)-mediated. These results demonstrate that BDO2 induces cell cycle perturbation and arrest even with short-term exposure that does not produce other pathologic cellular effects.
Michael Schmiederer; Eugene Knutson; Perpetua Muganda; Thomas Albrecht
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Environmental and molecular mutagenesis     Volume:  45     ISSN:  0893-6692     ISO Abbreviation:  Environ. Mol. Mutagen.     Publication Date:  2005 May 
Date Detail:
Created Date:  2005-04-27     Completed Date:  2005-07-12     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  8800109     Medline TA:  Environ Mol Mutagen     Country:  United States    
Other Details:
Languages:  eng     Pagination:  354-64     Citation Subset:  IM    
Copyright Information:
Copyright 2005 Wiley-Liss, Inc
Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, Texas 77555, USA.
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MeSH Terms
Acute Toxicity Tests
Cell Cycle / drug effects*
Cell Cycle Proteins / analysis,  biosynthesis
Cell Nucleus / drug effects,  metabolism
Cell Proliferation / drug effects*
Cells, Cultured
Cyclin-Dependent Kinase Inhibitor p21
Dose-Response Relationship, Drug
Epoxy Compounds / toxicity*
G1 Phase / drug effects
G2 Phase / drug effects
Lung / drug effects*,  metabolism
Mitotic Index
Mutagens / toxicity*
Tumor Suppressor Protein p53 / analysis,  biosynthesis
Grant Support
Reg. No./Substance:
0/CDKN1A protein, human; 0/Cell Cycle Proteins; 0/Cyclin-Dependent Kinase Inhibitor p21; 0/Epoxy Compounds; 0/Mutagens; 0/Tumor Suppressor Protein p53; 1464-53-5/erythritol anhydride

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

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