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The proliferation test with human estrogen receptor-positive MCF-7 breast cancer cells (E-Screen assay) was applied for quantitative determination of total estrogenic activity in 24-h composite effluent samples from 16 municipal and two industrial sewage treatment plants (STPs) in the state of Baden-Württemberg, southwestern Germany. The estrogenic efficacy relative to the positive control, 17beta-estradiol, was between 26 and 74% (median, 48%) for the 16 municipal STPs. Estradiol equivalent concentrations (EEQs) were between 0.2 and 7.8 ng/L (median, 1.6 ng/L) and, thereby, were lower than those found in a pilot study, which revealed EEQs of greater than 10 ng/L in the effluents of two other STPs. The EEQs in 14 of the 16 effluent samples were very similar (0.9-3.3 ng/L), indicating a rather constant input of estrogenic substances via STPs into rivers. Additional activated charcoal filtration turned out to be very efficient in further eliminating estrogenic activity from effluents. The EEQs of the E-Screen assay and those calculated from the results of extensive chemical analysis using the estradiol equivalency factors determined for 13 natural and synthetic estrogenic substances were comparable for most of the effluent samples. 17beta-Estradiol, 17alpha-ethinylestradiol, and, to a lesser extent, estrone contributed to 90% or more of the EEQ value.

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UVR suppresses the immune system through the induction of regulatory T cells (Tregs). UVR-induced DNA damage has been recognized as the major molecular trigger involved, as reduction of DNA damage by enhanced repair prevents the compromise to the immune system by UVR. Nevertheless, other signaling events may also be involved. The aryl hydrocarbon receptor (AhR) was identified as another target for UVR, as UVR activates the AhR and certain UVR effects were not detected in AhR-deficient cells. We studied whether the AhR is involved in UVR-induced local immunosuppression and whether similar effects can be induced by AhR agonists. The AhR antagonist 3-methoxy-4-nitroflavone reduced UVR-mediated immunosuppression and the induction of Tregs in murine contact hypersensitivity (CHS). Conversely, activation of the AhR by the agonist 4-n-nonylphenol (NP) suppressed the induction of CHS and induced antigen-specific Tregs similar to UVR. This was further confirmed in AhR knockout mice in which UVR- and NP-induced immunosuppression were significantly reduced. Together, this indicates that the AhR is involved in mediating UVR-induced immunosuppression. Activation of the AhR might represent an alternative to modulate the immune system in a similar manner like UVR but without causing the adverse effects of UVR, including DNA damage.