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

Toxicology. 2004 Jul 1;199(2-3):109-20. doi: 10.1016/j.tox.2004.02.015.

Abstract

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 microM). The uterotrophic assay of 3-BC (oral gavage) in immature rats showed unexpected potency with ED50 45.3mg/kg per day; lowest effective dose 2mg/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 16alpha 125I-estradiol from porcine uterine cytosolic receptors (IC(50): 14.5 and 112 microM), and from recombinant human estrogen receptor beta (hERbeta) (IC(50): 3-BC, 11.8 microM; 4-MBC, 35.3 microM), whereas no displacement was detected at human estrogen receptor alpha (hERalpha) up to 3mM. This subtype selectivity makes the two camphor derivatives interesting model compounds. Their activity on immature rat uterus is not easily explained by ERbeta activation. It cannot be excluded that active metabolites with possibly different receptor binding characteristics are formed in vivo.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Animals
  • Benzhydryl Compounds
  • Breast Neoplasms / drug therapy
  • Breast Neoplasms / metabolism
  • Camphor / analogs & derivatives*
  • Camphor / pharmacology*
  • Cell Division / drug effects
  • Cell Line, Tumor
  • Estradiol / pharmacology
  • Estrogen Receptor beta
  • Estrogens, Non-Steroidal / pharmacology*
  • Ethinyl Estradiol / pharmacology
  • Female
  • Genistein / pharmacology
  • Humans
  • Organ Size / drug effects
  • Phenols / pharmacology
  • Rats
  • Rats, Long-Evans
  • Receptors, Estrogen / metabolism*
  • Sunscreening Agents / pharmacology*
  • Swine
  • Uterus / drug effects*
  • Uterus / metabolism

Substances

  • Benzhydryl Compounds
  • Estrogen Receptor beta
  • Estrogens, Non-Steroidal
  • Phenols
  • Receptors, Estrogen
  • Sunscreening Agents
  • Ethinyl Estradiol
  • Estradiol
  • Camphor
  • enzacamene
  • Genistein
  • bisphenol A