Estrogen-like effects of ultraviolet screen 3-(4-methylbenzylidene)-camphor (Eusolex 6300) on cell proliferation and gene induction in mammalian and amphibian cells.
We tested the ultraviolet screen 3-(4-methylbenzylidene)-camphor (4-MBC; Eusolex 6300), which has been implicated as a potential endocrine disruptor, for its potential to bind to and activate endogenous estrogen receptors (ER) and to mediate ER-dependent changes in gene transcription, in hepatocytes of the water-dwelling South African clawed frog Xenopus laevis. We were able to confirm previous findings that 4-MBC accelerates cell proliferation in estrogen-dependent human breast cancer cells (MCF-7). Results of competitive binding assays of [3H]17beta-estradiol and 4-MBC using cytosolic protein preparations from Xenopus hepatocytes indicated that 4-MBC weakly binds to the ER. 4-MBC at a concentration of 100 micromol/L is not able to completely replace estradiol from the receptor. However, when 4-MBC was tested in a gene induction assay using the relative amount of ER transcript as a marker for ER-dependent transcriptional activation, we found that micromolar concentrations of this substance produced an increase in the amount of ER mRNA that was not different from the amount of mRNA that was observed upon activation of cells with 17beta-estradiol in concentrations above 1 nmol/L. The results indicate that 4-MBC has the potential to change physiological and developmental processes mediated by ER signaling mechanisms. It may therefore be a potentially harmful substance for water-dwelling animals when present in the environment at micromolar concentrations.
Klann
Anja
A
Zoological Institute, Ernst Moritz Arndt-University, JS Bach-Strasse 11/12, D-17487 Greifswald, Germany.
Levy
Gregor
G
Lutz
Ilka
I
Müller
Christian
C
Kloas
Werner
W
Hildebrandt
Jan-Peter
JP
D000818:Animals; D002164:Camphor / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology*; D045744:Cell Line, Tumor / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004958:Estradiol / Q000494:pharmacology; D005260:Female; D022781:Hepatocytes / Q000187:drug effects*; D006801:Humans; D008297:Male; D012333:RNA, Messenger / Q000187:drug effects; D011960:Receptors, Estrogen / Q000187:drug effects* / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013473:Sunscreening Agents / Q000008:administration & dosage / Q000494:pharmacology*; D014982:Xenopus laevis
D012333:RNA, Messenger; D011960:Receptors, Estrogen; D013473:Sunscreening Agents; D004958:Estradiol; D002164:Camphor; C038939:enzacamene