Activation of estrogen receptor alpha and ERbeta by 4-methylbenzylidene-camphor in human and rat cells: comparison with phyto- and xenoestrogens.
Toxicol Lett
; 142(1-2): 89-101, 2003 Apr 30.
Article
en En
| MEDLINE
| ID: mdl-12765243
ABSTRACT
4-Methylbenzylidene-camphor (4-MBC) is an organic sunscreen that protects against UV radiation and may therefore help in the prevention of skin cancer. Recent results on the estrogenicity of 4-MBC have raised concerns about a potential of 4-MBC to act as an endocrine disruptor. Here, we investigated the direct interaction of 4-MBC with estrogen receptor (ER) alpha and ERbeta in a series of studies including receptor binding, ER transactivation and functional tests in human and rat cells. 4-MBC induced alkaline phosphatase activity, a surrogate marker for estrogenic activity, in human endometrial Ishikawa cells. Interestingly, 4-MBC induced weakly ERalpha and with a higher potency ERbeta mediated transactivation in Ishikawa cells at doses more than 1 microM, but showed no distinct binding affinity to ERalpha or ERbeta. In addition, 4-MBC was an effective antagonist for ERalpha and ERbeta. In an attempt to put 4-MBC's estrogenic activity into perspective we compared binding affinity and potency to activate ER with phyto- and xenoestrogens. 4-MBC showed lower estrogenic potency than genistein, coumestrol, resveratrol, bisphenol A and also camphor. Analysis of a potential metabolic activation of 4-MBC that could account for 4-MBC's more distinct estrogenic effects observed in vivo revealed that no estrogenic metabolites of 4-MBC are formed in primary rat or human hepatocytes. In conclusion, we were able to show that 4-MBC is able to induce ERalpha and ERbeta activity. However, for a hazard assessment of 4-MBC's estrogenic effects, the very high doses of 4-MBC required to elicit the reported effects, its anti-estrogenic properties as well as its low estrogenic potency compared to phytoestrogens and camphor has to be taken into account.
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Bases de datos:
MEDLINE
Asunto principal:
Protectores Solares
/
Compuestos de Bencilideno
/
Alcanfor
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Receptores de Estrógenos
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Antagonistas de Estrógenos
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Estrógenos
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Isoflavonas
Límite:
Animals
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Female
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Humans
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Male
Idioma:
En
Revista:
Toxicol Lett
Año:
2003
Tipo del documento:
Article
País de afiliación:
Alemania