Details

Autor(en) / Beteiligte

• Schlumpf, Margret
• Jarry, Hubert
• Wuttke, Wolfgang
• Ma, Risheng
• Lichtensteiger, Walter

Titel

Estrogenic activity and estrogen receptor β binding of the UV filter 3-benzylidene camphor: Comparison with 4-methylbenzylidene camphor

Ist Teil von

• Toxicology (Amsterdam), 2004-07, Vol.199 (2), p.109-120

Ort / Verlag

Shannon: Elsevier Ireland Ltd

Erscheinungsjahr

2004

Quelle

MEDLINE

Beschreibungen/Notizen

• UV filters represent new classes of estrogenic [Environ. Health Perspect. 109 (2001) 239] or antiandrogenic [Toxicol. Sci. 74 (2003) 43] chemicals. We tested 3-benzylidene camphor (3-BC), reported as estrogenic in fish [Pharmacol. Toxicol. 91 (2002) 204], and mammalian systems in comparison to 4-methylbenzylidene camphor (4-MBC), shown to be active in rats, and analyzed binding to estrogen receptor subtypes. 3-BC and 4-MBC stimulated MCF-7 cell proliferation (EC 50: 0.68 and 3.9 μM). The uterotrophic assay of 3-BC (oral gavage) in immature rats showed unexpected potency with ED50 45.3 mg/kg per day; lowest effective dose 2 mg/kg per day, and maximum effect with 70% of ethinylestradiol. After comparing with literature data, we found that the oral 3-BC was considerably more potent than oral bisphenol A and almost as active as subcutaneous genistein. 3-BC and 4-MBC displaced 16α 125I-estradiol from porcine uterine cytosolic receptors (IC 50: 14.5 and 112 μM), and from recombinant human estrogen receptor β (hERβ) (IC 50: 3-BC, 11.8 μM; 4-MBC, 35.3 μM), whereas no displacement was detected at human estrogen receptor α (hERα) up to 3 mM. This subtype selectivity makes the two camphor derivatives interesting model compounds. Their activity on immature rat uterus is not easily explained by ERβ activation. It cannot be excluded that active metabolites with possibly different receptor binding characteristics are formed in vivo.