diethylstilboestrol

Concerned with the high incidence of breast and prostate cancers in industrialized countries, including France, we reviewed the literature and national reports on the potential carcinogenic effects of several endocrine disruptors (ED) present in the environment. We examine why it is extremely difficult to obtain clear proof of a carcinogenic effect of ED in humans. Yet the results of several independent studies strongly point to such a carcinogenic effect, particularly in the case of hormone-dependent cancers...

Reference genotoxic compounds 2-aminoanthracene, diethylstilboestrol and vinblastine were tested in the in vitro micronucleus assay using Chinese hamster V79 derived cells in the laboratories of British American Tobacco in the UK. The work was conducted in support of the cytotoxicity measures recommended in the 2007 version of the OECD Test Guideline 487. The three compounds were positive in the assay in the presence and absence of the cytokinesis blocking agent cytochalasin B at concentrations that did not exceed the recommended cytotoxic limits determined by relative population doubling, relative increase in cell counts, relative cell counts and cytokinesis block proliferation index...

This study investigated the effect on the uterus of the aqueous fraction of the partitioned methanol crude extract of the leaves of Anthocleista djalonensis (AD) and the possible mechanism of AD activity. AD inhibited the concentration-response curves induced by oxytocin and CaCl2 on the rat uterus in vitro and significantly reduced the EC50 in a concentration-dependent manner (p < 0.05). A similar effect was observed with salbutamol and verapamil on the concentration-response curves obtained for oxytocin and CaCl2...

Quercetin has been reported to be an efficient antioxidant which protects chicken spermatogonial cells from oxidative damage through increasing intracellular antioxidants and decreasing lipid peroxidation. Exposure to diethylstilboestrol (DES) could cause reproductive damage in males, which is associated with oxidative stress. This study was conducted to investigate the protective effects of quercetin on DES-induced oxidative damage in cultured hamster spermatogenic cells. The cells were treated with different concentrations of DES, and their growth status was observed under inverted microscope...

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Much work has been done in vivo on the effects of sex steroids on the developing foetus. Many genital anomalies have been reported; defects of other organ systems have been suggested. Synthetic oestrogens are considered to be developmental toxicants in vivo, while natural oestrogens are thought to present little or no risk. A small selection of hormones (17beta-oestradiol, 17alpha-ethynyloestradiol, diethylstilboestrol and progesterone) was tested using the rat whole embryo culture technique to see whether this difference could also be confirmed in vitro...

Recently, primary cultures consisting mostly of fibroblasts and up to 8% epithelial cells have been derived from ram seminal vesicles (SEMV), which contain high levels of prostaglandin H synthase (PHS). PHS-peroxidase can catalyse the metabolic activation of several xenobiotics, for example diethylstilboestrol (DES). Thus SEMV cells can be a useful tool for investigating whether PHS has a role in mediating the adverse genotoxic effects of such substances, provided that a suitable endpoint for genotoxicity can be determined in this model system...

The synthetic oestrogen diethylstilboestrol (DES) causes a dose-dependent elevation of the cytoplasmic Ca(2+) concentration in C6 rat glioma cells. This Ca(2+) rise is caused neither by Ca(2+) influx nor by release from the Ca(2+) stores of the endoplasmic reticulum. Therefore it seems likely that DES mobilizes Ca(2+) from a mitochondrial source. The DES-induced Ca(2+) signal is remarkably similar to the one induced by the tumour promotor thapsigargin. As this compound causes leakage of calcium from the endoplasmic reticulum it seems possible that DES induces a similar leakage from mitochondrial Ca(2+) stores...

The responses of human and rodent cells in vitro to aneuploidy-inducing chemicals were compared. Normal human fibroblasts and Syrian hamster embryo fibroblasts were treated with four aneuploidogens; Colcemid, vincristine, and the oestrogens diethylstilboestrol and oestra-1,3,5(10)-triene-3,17beta-diol (17beta-oestradiol). All compounds at a critical dose inhibited cell growth of both cell types. The concentrations of the two oestrogens required to inhibit growth of human and hamster cells were similar, whereas for the two mitotic inhibitors Colcemid and vincristine, the concentrations required for growth-inhibitory effects were lower for human cells than for hamster cells...

Carcinogen-induced nuclear enlargement has been reported both in vitro and in vivo, but the mechanism, and whether it is causally related to carcinogenesis, has not yet been established. This study was designed to investigate the role of increased DNA content, such as might occur in polyploidy, in induction of nuclear enlargement. The effects of two genotoxic carcinogens, N-methyl-N-nitrosourea and adriamycin, were compared with the effects induced by diethylstilboestrol, which is arguably a non-genotoxic carcinogen but is known to induce polyploidy...

Two analogues of the carcinogenic oestrogen diethylstilboestrol (DES), indenoestrol A (IA) and indenoestrol B (IB), have been studied with respect to their genotoxic and cell transforming properties in mammalian cells. The conformation and oestrogenicity of IA and IB are very similar, but they differ with respect to their ease of peroxidation and the resulting reactive intermediates: only IA is readily converted to a p-quinone. Both DES derivatives caused morphological transformation of Syrian hamster embryo (SHE) fibroblasts with similar efficiency at concentrations (1 to 10 mum) that did not affect cloning efficiency...

A European collaborative study was conducted in order to investigate the different measurements of cytotoxicity assessment in the in vitro micronucleus test. Relative population doubling and relative increase in cell counts were the measurements of cytotoxicity assessed in this study. The test chemicals, etoposide, benzo[a]pyrene, cytosine arabinoside and diethylstilboestrol were tested in this in vitro micronucleus assay, in mouse lymphoma L5178Y cells, without cytokinesis block. This study was conducted in support of the toxicity measurements recommended in the draft OECD Test Guideline 487...

Pig hepatocytes were used for determining the cytotoxicity of a number of veterinary drugs and known hepatotoxic compounds, using the MTT test as a marker for viability. When possible, drugs were tested in the absence and presence of dimethyl sulfoxide (DMSO), to study the possible effect of this solvent when used in the case of less hydrophilic compounds. IC(50) values calculated from the dose-response curves for acetylsalicylic acid (7 mm) and acetaminophen (paracetamol; 10 mm) in rat hepatocytes were similar to those reported by other groups...

The aneuploidy-inducing carcinogenic oestrogen diethylstilboestrol (DES) causes an elevation of the cytoplasmic Ca(2+) concentration of C6 rat glioma cells. It is known that the intracellular calcium concentration is a critical factor in mitosis. DES induces mitotic disturbances resulting in aneuploidy; the mechanisms of these events are still largely unknown. It is therefore important to identify the calcium source for the DES-mediated calcium rise. Experiments with isolated rat liver mitochondria showed no release of calcium after DES treatment...

Diethylstilboestrol 5 mg tid x 5 days has proven effective in preventing pregnancy in a small series of girls of child-bearing age who had unprotected intercourse and who presented themselves within 48 hours. The author suggests that this therapy would be applicable to women on contraception who err in taking their medication.

This study summarises the results of four different chemicals evaluated for induction of micronuclei (MN) in L5178Y tk(+/-) cells in the absence of cytochalasin B. All four chemicals (the tubulin polymerisation inhibitor Colchicine, Diethylstilboestrol which inhibits both tubulin polymersation as well as depolymerisation, the cross-linking agent Mitomycin C and Cyclophosphamide which requires metabolism to form the ultimate mutagen) showed biologically and statistically significant induction in MN frequency compared to concurrent controls...

The reference genotoxic agents Cytosine arabinoside, Vinblastine, Diethylstilboestrol and 2-Aminoanthracene were tested in the in vitro micronucleus assay, in human lymphoblastoid TK6 cells, without cytokinesis block, at the laboratories of Institut Pasteur de Lille, France. This was done in support of the toxicity measures recommended in the late 2007 version of the draft OECD Test Guideline 487 for the testing of chemicals. All four reference agents were positive in the assay at concentrations giving approximately 50% toxicity or less as assessed by draft Test Guideline 487 recommended measures, relative population doublings and relative increase in cell counts...

No abstract text is available yet for this article.

No abstract text is available yet for this article.

No abstract text is available yet for this article.