endocrine disruption

/Tag:endocrine disruption

Oestradiol Potentiates the Effects of Certain Pyrethroid Compounds in the MCF7 Human Breast Carcinoma Cell Line

Irma Kakko, Tarja Toimela and Hanna Tähti

Pyrethroids are the most widely used insecticides for indoor pest control, so human exposure to them is common. The main target of pyrethroids is the nervous system, but their endocrine disrupting capabilities may also be of toxicological concern. In the present study, the proliferation of the breast cancer cell line, MCF7, was studied after a 7-day exposure to various concentrations of pyrethrin, permethrin and cypermethrin. The effects of oestradiol and the combined effects of oestradiol (0.10nM) and pyrethroids (0.1–100μM) on MCF7 cell proliferation were also evaluated. Proliferation and cell toxicity were studied by measuring the ATP content with a luminescence method, and mitochondrial metabolic enzyme activity with the WST-1 test. In the ATP test, low concentrations (0.1–1μM) of pyrethroids in co-exposure with oestradiol caused a clear statistically significant increase in the proliferation of MCF7 cells. This was evident when compared to the proliferative effect caused by 0.1nM oestradiol alone. High concentrations were cytotoxic, and the greatest cell toxicity was that of cypermethrin, which has a cyano group in its molecular structure.
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The Effects of Selected Phenol and Phthalate Derivatives on Steroid Hormone Production by Cultured Porcine Granulosa Cells

Alzbeta Mlynarcíková, Mária Ficková and Sona Scsuková

We have investigated the effects of several phenols (octylphenol [OP], nonylphenol [NP], tertoctylphenol [tOP]) and phthalates (dioctylphthalate [DOP], diisodecylphthalate [DiDP], diisononylphthalate [DiNP]) on steroid hormone production by porcine ovarian granulosa cells after a 72-hour incubation. These chemicals are widely used as plasticisers and are suspected to possess endocrine disrupting properties. No changes were exhibited in basal progesterone production after treatment with NP or tOP, or with the tested phthalates. However, OP tended to decrease progesterone levels, while DOP and DiDP, at the lowest concentration used (10–8M), increased progesterone levels in the culture media. Neither of the tested phenols affected follicle stimulating hormone (FSH)-stimulated progesterone production, except for OP and NP at 10–4M, which decreased progesterone levels. The phthalates, tested at higher concentrations, were able to amplify FSH-stimulated progesterone release into the culture medium. An inhibitory action on oestradiol production by porcine granulosa cells was observed after the treatment with both groups of test chemicals. The results obtained in the experiments on primary granulosa cell cultures indicate that ovarian steroidogenesis might be one of the possible sites affected by the endocrine disrupting actions of phenols and phthalates.
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In Silico Toxicology in Drug Discovery — Concepts Based on Three-dimensional Models

Angelo Vedani and Martin Smiesko

Animal testing is still compulsory worldwide, for the approval of drugs and chemicals produced in large quantities. Computer-assisted (in silico) technologies are considered to be efficient alternatives to in vivo experiments, and are therefore endorsed by many regulatory agencies, e.g. for use in the European REACH initiative. Advantages of in silico methods include: the possible study of hypothetical compounds; their low cost; and the fact that such virtual experiments are typically based on human data, thus making the question of interspecies transferability obsolete. Since the mid-1990s, computer-based technologies have become an indispensable tool in drug discovery — used primarily to identify small molecules displaying a stereospecific and selective binding to a regulatory macromolecule. Since toxic effects are still responsible for some 20% of the late-stage failures, there is a continuing need for in silico concepts which can be used to estimate a compound’s ADMET (adsorption, distribution, metabolism, elimination, toxicity) properties — in particular, toxicity. The aim of this paper is to provide an insight into computational technologies that allow for the prediction of toxic effects triggered by pharmaceuticals. As most adverse and toxic effects are mediated by unwanted interactions with macromolecules involved in biological regulatory systems, we have focused on methodologies that are based on three-dimensional models of small molecules binding to such entities, and discuss the results at the molecular level.
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Chlorotriazines Do Not Activate the Aryl Hydrocarbon Receptor, the Oestrogen Receptor or the Thyroid Receptor in In Vitro

Irene de la Casa-Resino, José M. Navas and María L. Fernández-Cruz