Zusammenfassung
Die in den letzten Jahren offenbar zunehmenden hormonbedingten Störungen bei Mensch und Tier sowie das vermehrte Auftreten hormonbedingter Krebsarten werden bisweilen mit Umweltchemikalien in Verbindung gebracht, die im Verdacht stehen, die Wirkung natürlicher Hormone nachzuahmen bzw. zu blockieren. Für eine Reihe von Umweltchemikalien konnten endokrine Eigenschaften nachgewiesen werden. Über eine mögliche hormonelle Aktivität der derzeit in der Bundesrepublik Deutschland zugelassenen Pflanzenschutzmittel ist bislang wenig bekannt.
Ziel der vorliegenden Arbeit war die Untersuchung von insgesamt 57 Wirkstoffen von in der Bundesrepublik Deutschland zugelassenen Pflanzenschutzmitteln und Wachstumsreglern auf mögliche östrogene Aktivität in vitro mit Hilfe des E-Screen-Assays an der humanen Brustkrebszellinie MCF-7. Für insgesamt 8 der untersuchten Stoffe konnte eine rezeptorvermittelte östrogene Aktivität in vitro nachgewiesen werden. Mit Ausnahme einer Substanz zeigten 7 Stoffe eine sehr schwache Affinität zum humanen Östrogenrezeptor. Ihre Fähigkeit, 17β-Östradiol vom rezeptor zu verdrängen, war gering. Lediglich das Herbizid Pendimethalin ist als voller Östrogenrezeptor-Agonist einzustufen; es verdrängte 17β-Östradiol nahezu vollständig vom Rezeptor. Allerdings war die östrogene Potenz von Pendimethalin im Vergleich zu 17β-Östradiol, wie bei den anderen 7 positiv getesteten Substanzen auch, gering. Von diesen 7 Stoffen wurden zwei aufgrund ihrer schwachen Affinität zum humanen Östrogenrezeptor als nicht mehr östrogen wirksam eingestuft. In wie weit die hier vorliegenden Ergebnisse für lebende Organismen relevant sein können, muss in weiterführenden Untersuchungen in vivo geklärt werden.
Abstract
Over the last years, the obviously increasing, hormone-dependent impairments observed in humans and animals, as well as the increased occurrence of hormone-dependent types of cancer, are sometimes associated with environmental chemicals which are suspected to imitate or block the effects of natural hormones. For a variety of environmental chemicals an endocrine efficacy could already be demonstrated. Little is known, however, about a possible hormonal activity of plant protection agents which are at present certificated in the Federal Republic of Germany.
The aim of the present study was the in vitro testing of at least 57 active ingredients of pesticides and growth regulators certificated in the Federal Republic of Germany, for their possible estrogenic activity. The E-Screen-Assay based on the human breast cancer cell line MCF-7 was used as the suitable test system. For at least 8 of the tested substances, an receptor-mediated estrogenic activity could be shown in vitro. With the exception of one substance, 7 active ingredients displayed a very weak affinity for the human estrogen receptor. Their ability to displace 17β-estradiol from the receptor was low. Only the herbicide Pendimethalin is to be classified as a full estrogen receptor agonist; it is able to displace 17β-estradiol almost completely from the receptor. Howeverm the estrogenic potency of Pendimethalin, in comparison to 17β-estradiol, was seen to be as small as the estrogenic potency of the other 7 substances tested positively in the E-Screen-Assay. Among this 7 substances, two could not be classified as estrogenically active anymore, because their affinity to the human estrogen receptor was too weak. The relevance of the available results for livng organisms should be clarified in further in vivo investigations.
Abbreviations
- DMEM:
-
Dulbecco’s Modification of Eagle’s Medium
- DMSO:
-
Dimethylsulfoxid
- E2:
-
17β-Östradiol
- F:
-
Fungizid
- H:
-
Herbizid
- HEPES:
-
2-(4-(2-Hydroxyethyl)-1-piperazinyl)-ethansulfonsäure, I=Insektizid
- LH:
-
Luteinisierendes Hormon
- MCF:
-
Michigan Cancer Foundation
- PE:
-
Proliferativer Effekt
- RPE:
-
Relativer Proliferativer Effekt
- RPP:
-
Relative Proliferative Potenz
- TRIS:
-
2-Amino-2-(hydroxymethyl)-1,3-propandiol
- W:
-
Wachstumsreglet
- YES:
-
Yeast Estrogen Screen
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Dieser Artikel enthäit Teile der Dissertation von Nikola Bitsch
Gefördert vom Landesjagdverband Rheinland-Pfalz
OnlineFirst: 03.04.2002
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Bitsch, N., Körner, W., Failing, K. et al. In vitro Screening von Pflanzenschutzmittel-Wirkstoffen auf östrogene Aktivität. UWSF - Z Umweltchem Ökotox 14, 76–84 (2002). https://doi.org/10.1065/uwsf2002.04.016
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DOI: https://doi.org/10.1065/uwsf2002.04.016