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

Journal Article · Sat Nov 01 04:00:00 EDT 2008 · Toxicology and Applied Pharmacology

DOI:https://doi.org/10.1016/j.taap.2008.07.017· OSTI ID:21180449

Molina-Molina, Jose-Manuel ^[1]; Escande, Aurelie; Pillon, Arnaud ^[1]; Gomez, Elena ^[2]; Pakdel, Farzad ^[3]; Cavailles, Vincent ^[1]; Olea, Nicolas ^[4]; Ait-Aissa, Selim ^[5]; Balaguer, Patrick ^[1]

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1. IRCM, Institut de Recherche en Cancerologie de Montpellier, Montpellier, F-34298 (France)
2. Departement des sciences de l'Environnement et sante Publique, UMR 5569, Faculte de Pharmacie, Universite Montpellier I, Montpellier, F-34293 (France)
3. Endocrinologie Moleculaire de la reproduction, UMR CNRS 6026, Universite de Rennes I, Rennes, F-35042 (France)
4. Laboratory of Medical Investigations, San Cecilio University Hospital, University of Granada, Ciber en Epidemiologia y Salud Publica (CIBERESP), Granada, E-18071 (Spain)
5. INERIS, Unite Evaluation des Risques Ecotoxicologiques, Verneuil-en-Halatte, F-60550 (France)

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 (hER{alpha}), and there has been no comprehensive analysis of their potency in a system allowing comparison between hER{alpha} and hER{beta} 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 hER{alpha} and hER{beta} agonists (BP2 > THB > BP1) and displayed a stronger activation of hER{beta} compared with hER{alpha}, the opposite effect to that of estradiol (E{sub 2}). Unlike E{sub 2}, BPs were more active in rainbow trout ER{alpha} (rtER{alpha}) than in hER{alpha} 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 ER{beta} versus ER{alpha} activation, support further investigation of their role as endocrine disrupters in humans and wildlife.

• OSTI ID: 21180449
• Journal Information: Toxicology and Applied Pharmacology, Journal Name: Toxicology and Applied Pharmacology Journal Issue: 3 Vol. 232; ISSN TXAPA9; ISSN 0041-008X
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
ANDROGENS
BENZOPHENONE
BIOASSAY
CELL PROLIFERATION
CONSUMER PRODUCTS
DRUGS
ESTRADIOL
GENES
HAIR
IN VITRO
INDUCTION
LIVER CELLS
RECEPTORS
TROUT