Lack of activity of cadmium in in vitro estrogenicity assays

Journal Article · Sun Oct 01 00:00:00 EDT 2006 · Toxicology and Applied Pharmacology

DOI:https://doi.org/10.1016/j.taap.2006.04.002· OSTI ID:20850423

Silva, Elisabete ^[1]; Lopez-Espinosa, Maria Jose ^[2]; Molina-Molina, Jose-Manuel ^[2]; Fernandez, Marieta ^[2]; Olea, Nicolas ^[2]; Kortenkamp, Andreas ^[1]

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1. Centre for Toxicology, School of Pharmacy, University of London, 29-39 Brunswick Square, London WC1N 1AX (United Kingdom)
2. School of Medicine, Hospital Clinico, University of Granada, 18071-Granada (Spain)

Prompted by reports about strong estrogenic effects of cadmium, attempts were made to reproduce these observations using the yeast estrogen screen (YES) and the E-Screen assays. For the first time, possible activation of the Src/MAPK pathway was also investigated. In the YES, only a slight activation (10% of a maximal effect) of the estrogen receptor alpha (ER{alpha}) was observed at cadmium concentrations between 5 x 10{sup -7} M and 5 x 10{sup -6} M. In the E-Screen assay, carried out by two laboratories, the heavy metal was without observable cell proliferative effects when tested in the range between 6 x 10{sup -11} M and 1 x 10{sup -5} M. However, in both assays, cadmium led to a reduction of the effects of 17{beta}-estradiol (E2). Treatment of MCF-7 human breast cancer cells with 1 x 10{sup -7} M cadmium failed to induce phosphorylation of Src and the MAP kinases Erk1 and Erk2-effects shown to occur with E2 and epidermal growth factor (EGF). In summary, we were unable to confirm the strong estrogenicity of cadmium reported recently by a number of laboratories. This apparent absence of effects in our hands is not due to a lack of uptake of the metal or to effective protection against cadmium by high levels of glutathione or metallothionein, since toxicity and an antagonism of E2 responses were observed both in the YES and the E-Screen.

• OSTI ID: 20850423
• Journal Information: Toxicology and Applied Pharmacology, Vol. 216, Issue 1; Other Information: DOI: 10.1016/j.taap.2006.04.002; PII: S0041-008X(06)00123-2; Copyright (c) 2006 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA); ISSN 0041-008X
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
CADMIUM
CATTLE
CHARCOAL
DEXTRAN
ELECTROMECHANICS
ESTRADIOL
GLUTATHIONE
GROWTH FACTORS
HEAVY METALS
IN VITRO
MAMMARY GLANDS
METALLOTHIONEIN
NEOPLASMS
PHOSPHORYLATION
PHOSPHOTRANSFERASES
RECEPTORS
TOXICITY
UPTAKE
YEASTS