Tamoxifen prevents induction of hepatic neoplasia by zeranol, an estrogenic food contaminant.
Zeranol (alpha-zearalanol) is a beta-resorcylic acid lactone (RAL) that has estrogen activity. It is synthesized by molds and is difficult to avoid in human food products. We tested the ability of this mycoestrogen to damage the liver of the Armenian hamster, a rodent that is especially sensitive to hepatotoxic effects of exogenous estrogens. Zeranol induced acute hepatotoxicity and, subsequently, hepatic carcinogenesis; both effects were blocked by tamoxifen, suggesting estrogen receptor mediation. Because zeranol is acting alone as a primary initiator of hepatic neoplasms, this model provides an unusual opportunity to study the pathogenesis of estrogen-initiated tumorigenesis.
Coe
J E
JE
National Institutes of Health, National Institute of Allergy and Infectious Diseases, Hamilton, MT 59840.
Ishak
K G
KG
Ward
J M
JM
Ross
M J
MJ
D000818:Animals; D001663:Bilirubin / Q000097:blood; D006224:Cricetinae; D003412:Cricetulus; D004305:Dose-Response Relationship, Drug; D004967:Estrogens / Q000633:toxicity; D005260:Female; D005506:Food Contamination; D008113:Liver Neoplasms / Q000139:chemically induced* / Q000473:pathology; D008297:Male; D013629:Tamoxifen / Q000494:pharmacology*; D015029:Zeranol / Q000037:antagonists & inhibitors / Q000633:toxicity*
D004967:Estrogens; D013629:Tamoxifen; D015029:Zeranol; D001663:Bilirubin