Short communication Activation of estrogen receptor a and ERb by 4- methylbenzylidene-camphor in human and rat cells: comparison with phyto- and xenoestrogens

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) a and ERb 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 ERa and with a higher potency ERb mediated transactivation in Ishikawa cells at doses more than 1 mM, but showed no distinct binding affinity to ERa or ERb. In addition, 4-MBC was an effective antagonist for ERa and ERb. In an attempt to put 4-MBC’s estrogenic activity into perspective we compared binding affinity and potency to activate ER with phytoand 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 ERa and ERb 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. # 2003 Elsevier Science Ireland Ltd. All rights reserved.