Profiling of benzophenone derivatives using fish and human estrogen receptor-specific in vitro bioassays

Autor: José-Manuel Molina-Molina, Vincent Cavaillès, Patrick Balaguer, Elena Gomez, Nicolás Olea, Selim Ait-Aissa, Arnaud Pillon, Aurélie Escande, Farzad Pakdel
Přispěvatelé: Institut de recherche en cancérologie de Montpellier (IRCM - U896 Inserm - UM1), Université Montpellier 1 (UM1)-CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Laboratory of Medical Investigations, Universidad de Granada = University of Granada (UGR)-San Cecilio University Hospital, Hydrosciences Montpellier (HSM), Institut de Recherche pour le Développement (IRD)-Université Montpellier 2 - Sciences et Techniques (UM2)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS), Interactions cellulaires et moléculaires (ICM), Université de Rennes (UR)-Centre National de la Recherche Scientifique (CNRS), Institut National de l'Environnement Industriel et des Risques (INERIS), This research was supported by grants from the European Union Commission (EDEN QLK4-CT-2002-00603 and CASCADE FOOD-CT-2004-506319) and from the French Ministry of Ecology and Sustainable Development (PRG189-07-DRC01) to SA., Le Ster, Yves, CRLCC Val d'Aurelle - Paul Lamarque-Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Montpellier 1 (UM1), University of Granada [Granada]-San Cecilio University Hospital, Institut national des sciences de l'Univers (INSU - CNRS)-Institut de Recherche pour le Développement (IRD)-Université Montpellier 2 - Sciences et Techniques (UM2)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Centre National de la Recherche Scientifique (CNRS)
Rok vydání: 2008
Předmět:
MESH: Vitellogenins
Estrogen receptor
Estrogenic activity
Endocrine Disruptors
010501 environmental sciences
Toxicology
01 natural sciences
MESH: Dose-Response Relationship
Drug
Vitellogenins
MESH: Animals
Receptor
MESH: Estrogen Receptor alpha
Benzophenones (BPs)
MESH: Estrogen Receptor beta
0303 health sciences
Estradiol
Human androgen receptor (hAR)
Rainbow trout estrogen receptor alpha (rtERΑ)
Biological activity
Vitellogenin (Vtg)
MESH: Endocrine Disruptors
3. Good health
[SDV.TOX] Life Sciences [q-bio]/Toxicology
Reporter gene assay
Cell proliferation assay
MESH: Androgen Antagonists
MESH: Oncorhynchus mykiss
Endocrine disruptor
Oncorhynchus mykiss
[SDV.TOX]Life Sciences [q-bio]/Toxicology
Biological Assay
MESH: Estradiol
Receptor binding assay
medicine.medical_specialty
MESH: Benzophenones
Biology
MESH: Biological Assay
Benzophenones
03 medical and health sciences
Vitellogenin
MESH: Cell Proliferation
Internal medicine
medicine
Animals
Estrogen Receptor beta
Humans
Cell Proliferation
030304 developmental biology
0105 earth and related environmental sciences
Pharmacology
Reporter gene
MESH: Humans
Dose-Response Relationship
Drug
Estrogen Receptor alpha
Androgen Antagonists
Molecular biology
Androgen receptor
Endocrinology
biology.protein
Estrogen receptor alpha
Human estrogen receptor alpha and beta (hERα and hERβ)
Zdroj: Toxicology and Applied Pharmacology
Toxicology and Applied Pharmacology, 2008, 232 (3), pp.384-95. ⟨10.1016/j.taap.2008.07.017⟩
Toxicology and Applied Pharmacology, Elsevier, 2008, 232 (3), pp.384-95. ⟨10.1016/j.taap.2008.07.017⟩
ISSN: 0041-008X
1096-0333
DOI: 10.1016/j.taap.2008.07.017
Popis: International audience; Benzophenone (BP) derivatives, BP1 (2,4-dihydroxybenzophenone), BP2 (2,2',4,4'-tetrahydroxybenzophenone), BP3 (2-hydroxy-4-methoxybenzophenone), and THB (2,4,4'-trihydroxybenzophenone) are UV-absorbing chemicals widely used in pharmaceutical, cosmetics, and industrial applications, such as topical sunscreens in lotions and hair sprays to protect skin and hair from UV irradiation. Studies on their endocrine disrupting properties have mostly focused on their interaction with human estrogen receptor alpha (hERalpha), and there has been no comprehensive analysis of their potency in a system allowing comparison between hERalpha and hERbeta activities. The objective of this study was to provide a comprehensive ER activation profile of BP derivatives using ER from human and fish origin in a battery of in vitro tests, i.e., competitive binding, reporter gene based assays, vitellogenin (Vtg) induction in isolated rainbow trout hepatocytes, and proliferation based assays. The ability to induce human androgen receptor (hAR)-mediated reporter gene expression was also examined. All BP derivatives tested except BP3 were full hERalpha and hERbeta agonists (BP2>THB>BP1) and displayed a stronger activation of hERbeta compared with hERalpha, the opposite effect to that of estradiol (E2). Unlike E2, BPs were more active in rainbow trout ERalpha (rtERalpha) than in hERalpha assay. All four BP derivatives showed anti-androgenic activity (THB>BP2>BP1>BP3). Overall, the observed anti-androgenic potencies of BP derivatives, together with their proposed greater effect on ERbeta versus ERalpha activation, support further investigation of their role as endocrine disrupters in humans and wildlife.
Databáze: OpenAIRE
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