Sodium arsenite alters cell cycle and MTHFR, MT1/2, and c-Myc protein levels in MCF-7 cells

Journal Article · Tue Dec 15 00:00:00 EST 2009 · Toxicology and Applied Pharmacology

DOI:https://doi.org/10.1016/j.taap.2009.09.006· OSTI ID:21344809

Ruiz-Ramos, Ruben ^[1]; Lopez-Carrillo, Lizbeth ^[1]; Albores, Arnulfo ^[2]; Hernandez-Ramirez, Raul U ^[1]

---

1. Centro de Investigacion en Salud Poblacional, INSP, Cuernavaca, Morelos (Mexico)
2. Departamento de Toxicologia, Centro de Investigacion y de Estudios Avanzados del Instituto Politecnico Nacional, 07360 Mexico D.F. (Mexico)

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 muM) 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 muM) induced cell proliferation, showing a high proportion of BrdU-stained cells, indicating a higher DNA synthesis rate. However, higher concentrations (>= 5 muM) 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.

• OSTI ID: 21344809
• Journal Information: Toxicology and Applied Pharmacology, Vol. 241, Issue 3; Other Information: DOI: 10.1016/j.taap.2009.09.006; PII: S0041-008X(09)00387-1; Copyright (c) 2009 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; ISSN 0041-008X
• Country of Publication: United States
• Language: English

Related Subjects

63 RADIATION, THERMAL, AND OTHER ENVIRONMENTAL POLLUTANT EFFECTS ON LIVING ORGANISMS AND BIOLOGICAL MATERIALS
APOPTOSIS
ARSENIC
ARSENIC COMPOUNDS
CELL CYCLE
CELL PROLIFERATION
DNA
DOSES
ENZYMES
GENES
MAMMARY GLANDS
NEOPLASMS
SODIUM COMPOUNDS
SYNTHESIS
ALKALI METAL COMPOUNDS
BODY
DISEASES
ELEMENTS
GLANDS
NUCLEIC ACIDS
ORGANIC COMPOUNDS
ORGANS
PROTEINS
SEMIMETALS