Document Detail


Sodium arsenite alters cell cycle and MTHFR, MT1/2, and c-Myc protein levels in MCF-7 cells.
MedLine Citation:
PMID:  19766132     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
There is limited available information on the effects of arsenic on enzymes participating in the folate cycle. Therefore, our aim was to evaluate the effects of sodium arsenite on the protein levels of methylenetetrahydrofolate reductase (MTHFR) and dihydrofolate reductase (DHFR) and its further relationship with the expression MT1/2 and c-myc in MCF-7 cells. Arsenite treatment (0-10 microM) for 4 h decreased MTHFR levels in a concentration-dependent fashion without significant effects on DHFR. The effects on MTHFR were observed at arsenite concentrations not significantly affecting cell viability. We also observed an increase in S-phase recruitment at all concentrations probed. Lower concentrations (<5 microM) induced cell proliferation, showing a high proportion of BrdU-stained cells, indicating a higher DNA synthesis rate. However, higher concentrations (> or =5 microM) or longer treatment periods induced apoptosis. Arsenite also induced dose-dependent increases in MT1/2 and c-Myc protein levels. The levels of MTHFR were inversely correlated to MT1/2 and c-Myc overexpression and increased S-phase recruitment. Our findings indicate that breast epithelial cells are responsive to arsenite and suggest that exposure may pose a risk for breast cancer. The reductions in MTHFR protein levels contribute to understand the mechanisms underlying the induction of genes influencing growth regulation, such as c-myc and MT1/2. However, further research is needed to ascertain if the effects here reported following short-time and high-dose exposure are relevant for human populations chronically exposed to low arsenic concentrations.
Authors:
Ruben Ruiz-Ramos; Lizbeth López-Carrillo; Arnulfo Albores; Raúl U Hernández-Ramírez; Mariano E Cebrian
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2009-09-17
Journal Detail:
Title:  Toxicology and applied pharmacology     Volume:  241     ISSN:  1096-0333     ISO Abbreviation:  Toxicol. Appl. Pharmacol.     Publication Date:  2009 Dec 
Date Detail:
Created Date:  2009-11-09     Completed Date:  2009-12-02     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0416575     Medline TA:  Toxicol Appl Pharmacol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  269-74     Citation Subset:  IM    
Affiliation:
Centro de Investigación en Salud Poblacional, INSP, Cuernavaca, Morelos, México.
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MeSH Terms
Descriptor/Qualifier:
Antimetabolites / diagnostic use
Arsenites / toxicity*
Blotting, Western
Bromodeoxyuridine / diagnostic use
Cell Cycle / drug effects*
Cell Line, Tumor
Cell Survival / drug effects
Female
Flow Cytometry
Gene Expression / drug effects
Humans
Metallothionein / biosynthesis*
Methylenetetrahydrofolate Reductase (NADPH2) / biosynthesis*
Proto-Oncogene Proteins c-myc / biosynthesis*
S Phase / drug effects
Sodium Compounds / toxicity*
Chemical
Reg. No./Substance:
0/Antimetabolites; 0/Arsenites; 0/Proto-Oncogene Proteins c-myc; 0/Sodium Compounds; 13768-07-5/sodium arsenite; 59-14-3/Bromodeoxyuridine; 9038-94-2/Metallothionein; EC 1.5.1.20/Methylenetetrahydrofolate Reductase (NADPH2)

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


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