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[en] Estrone (E1), 17β-estradiol (E2), estriol (E3), equilin (EQ) and 17α-estradiol (17α) estrogen hormones are released by humans and animals and have been detected in the environment and municipal wastewater treatment plants. The structural and electronic properties of natural hormone molecules are investigated by performing density functional theory calculations and used to predict their properties and chemical behavior. Quantitative structure property relationship (QSPR) approach is applied to correlate the estrogenicity associated with the natural estrogen hormones according to their molecular properties. The obtained relationship reveals the importance of the frontier molecular orbital energy in the interpretation of estrogenic activity of hormones, which is consistent with the previous research. Moreover, the obtained molecular descriptors also aid determination of the degradability of hormones, and to rationalize degradation pathways, with chemical oxidizers such as ozone and hydroxyl radical. Both types of interactions belong to the orbital-controlled reactions. The active sites determined by Fukui functions for the estrogen hormone molecules confirm the reaction pattern that initiates the attack of the aromatic ring for both ozone and hydroxyl radical. The reactive sites of the molecules are mapped with subsequent reaction intermediates and compared with experimental data obtained from the literature. - Highlights: ►DFT methods described in this paper are suitable for predicting the degradation behavior of natural estrogen hormones. ►Using QSAR, the estrogenicity of natural hormones was determined by DFT descriptors. ►The sites of primary ozone and hydroxyl radical attack were predicted using DFT, and findings confirmed by experimental data.

[en] Estramustine phosphate (EMP), a nor-nitrogen mustard carbamate derivative of estradiol-17β-phosphate, causes G₂/M phase arrest in treated cells through its specific binding to microtubule associated proteins. Since cells in the G₂/M phase are the most radiosensitize, cell culture experiments were performed to determine whether EMP would enhance the radiosensitivity of related human tumor cells. A Phase II prospective study of concomitant radiotherapy (RT) and EMP plus Velban for locally advanced carcinoma of the prostate was carried out. Three established human tumor cells, DU-145 cells (prostate), MCF-7 cells (breast), and U-251 cells (malignant glioma), were used to determine cell survival curves with and without the drug. Flow cytometry was used to obtain the cell cycle distribution of cells that were exposed to the drug for periods of 1 day to 1 week. Patients with locally advanced prostate cancer were entered into the Phase II study. All patients received a total tumor dose of 65-70 Gy over 7 weeks. Oral EMP was administered daily and Velban was administered weekly, concomitantly during the course of RT. Radiosensitization was dependent on the exposure time and the drug concentration prior to radiation. No radiosensitization was obtained when cells were exposed to the drug after irradiation. The enhancement ratios varied from 1.3-1.6 at the 10% survival level. All patients who received the combined RT and EMP plus Velban achieved complete response. The rate of PSA (prostate specific antigen) reduction was very prompt compared to that of the RT alone group. There were no disproportionately enhanced side effects for the combined regimen. EMP enhances radiation induced cytotoxicity in several human tumor cells in culture. The effect is most significant after prolonged exposure to the drug before irradiation. Documented G₂/M phase cell cycle block by EMP is the likely mechanism of radiosensitization. 9 refs., 2 figs., 1 tab

No abstract available

[en] Endocrine disrupting chemicals, such as the free estrogens 17β-estradiol (E2), estrone (E1) and the conjugated estrogen estrone-sulfate (E1-3S) are found at low concentration levels in the environment. This is somehow contradictory to the strong sorption and high degradation potentials found in laboratory experiments. In particular, the fate and transport behavior of conjugated estrogens is poorly understood, and the importance of enzymes triggering the transformation pathways has received little attention. To address these deficiencies, the present research uses packed laboratory soil columns with pulse injections of free estrogens, either E2 or E1, or E1-3S, to provide sound evidence of the transformation pathways. It is further shown that (i) transport of free estrogens is subject to strong retardation and degradation, (ii) the transport of conjugated estrogens is less retarded and only to a minor degree affected by degradation, and (iii) arylsulfotransferase is the enzyme triggering the transformation reaction. - Highlights: • The transformation pathway of E2, E1 and E1-3S is explained for Bet Dagan soil. • Arylsulfotransferase (ASULT) is the relevant enzyme operating in Bet Dagan soil. • E1-3S forms after E2 or E1 injection in Bet Dagan soil. - The metabolic transformation pathway of E2, E1 and E1-3S in Bet Dagan soil has been clarified and the role of the enzyme arylsulfotransferase was identified.

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[en] Estrogen receptor (ER) transcriptional cross-talk after activation by 17β-estradiol (E2) has been studied in considerable detail, but comparatively little is known about the ways in which synthetic estrogen-like chemicals, so-called xenoestrogens, interfere with these signalling pathways. E2 can stimulate rapid, non-genomic signalling events, such as activation of the Src/Ras/Erk signalling pathway. We investigated how activation of this pathway by E2, the estrogenic environmental contaminants o,p'-DDT, β-HCH and p,p'-DDE, and epidermal growth factor (EGF) influences the expression of ER target genes, such as TFF1, ER, PR, BRCA1 and CCND1, and the proliferation of breast cancer cells. Despite commonalities in their estrogenicity as judged by cell proliferation assays, the environmental contaminants exhibited striking differences in their non-genomic and genomic signalling. The gene expression profiles of o,p'-DDT and β-HCH resembled the effects observed with E2. In the case of β-HCH this is surprising, considering its reported lack of affinity to the 'classical' ER. The expression profiles seen with p,p'-DDE showed some similarities with E2, but overall, p,p'-DDE was a fairly weak transcriptional inducer of TFF1, ER, PR, BRCA1 and CCND1. We observed distinct differences in the non-genomic signalling of the tested compounds. p,p'-DDE was unable to stimulate Src and Erk1/Erk2 activations. The effects of E2 on Src and Erk1/Erk2 phosphorylation were transient and weak when compared to EGF, but β-HCH induced strong and sustained activation of all tested kinases. Transcription of TFF1, ER, PR and BRCA1 by E2, o,p'-DDT and β-HCH could be suppressed partially by inhibiting the Src/Ras/Erk pathway with PD 98059. However, this was not seen with p,p'-DDE. Our investigations show that the cellular activities of estrogens and xenoestrogens are the result of a combination of extranuclear (non-genomic) and nuclear (genomic) events and highlight the need to take non-genomic effects and signalling cross-talk into consideration, when screening for environmental estrogens. Otherwise, chemicals devoid of ER affinity, such as β-HCH, but with an effect profile otherwise similar to estrogens might be overlooked in safety testing.

[en] The reliability of RIAs reported for phenolic steroids is frequently inferior relative to that for some other steroids, due to poor specificity of the antiserum used. In the present communication the production of highly specific antisera for oestradiol, oestrone and oestriol by 6-(O-carboxymethyl) oxime-BSA antigens and the radioimmunological methods elaborated for these steroids are reported. (orig.)

[en] We investigated the behavioral effects of exposure to waterborne phytoestrogens in male fighting fish, Betta splendens. Adult fish were exposed to a range of concentrations of genistein, equol, β-sitosterol, and the positive control 17β-estradiol. The following behaviors were measured: spontaneous swimming activity, latency to respond to a perceived intruder (mirror reflection), intensity of aggressive response toward a perceived intruder, probability of constructing a nest in the presence of a female, and the size of the nest constructed. We found few changes in spontaneous swimming activity, the latency to respond to the mirror, and nest size, and modest changes in the probability of constructing a nest. There were significant decreases, however, in the intensity of aggressive behavior toward the mirror following exposure to several concentrations, including environmentally relevant ones, of 17β-estradiol, genistein, and equol. This suggests that phytoestrogen contamination has the potential to significantly affect the behavior of free-living fishes. - Environmentally relevant concentrations of phytoestrogens reduce aggressive behavior in fish

No abstract available