WOOD-DERIVED ESTROGENS - STUDIES IN-VITRO WITH BREAST-CANCER CELL-LINES AND IN-VIVO IN TROUT

The wood-derived compound, beta-sitosterol (purity >90%), was shown to be estrogenic in fish. It induced the expression of the vitellogenin gene in the liver of juvenile and methyltestosterone-treated rainbow t rout. Structural similarities to p-sitosterol notwithstanding, cholest erol, citrostadienol, beta-sitostanol, and 5-androstene-3 beta,17 beta -diol, an estrogenic member of the androstenic steroid group, were ina ctive. An abietic acid mixture (37% abietic acid, 6% dehydroabietic ac id, and a remainder of unknown compounds) showed slight hormonal activ ity in feed, but it was completely inactive when given intraperitoneal ly in implants. The estrogenic component of the abietic acid preparati on was not identified. In addition to beta-sitosterol and abietic acid , several other wood-derived compounds including betulin, isorhapontig enin, isorhapontin, and pinosylvin were estrogenic in breast cancer ce lls (MCF-7 or T-47D). However, betulin and pinosylvin, available in su fficient amounts for in vivo testing, did not induce the expression of the vitellogenin gene. Differences in the primary sequences of human and fish estrogen receptors (hormone as well as DNA-binding regions) o r uptake and metabolism of the compounds may explain the discrepancy b etween the two estrogen bioassays. Wood-derived compounds such as beta -sitosterol, present in pulp and paper mill effluents, may account for the weak estrogenicity of debarking effluent seen at the vitellogenin expression bioassay. (C) 1996 Academic Press, Inc.