Tamoxifen prevents induction of hepatic neoplasia by zeranol, an estrogenic food contaminant

• Published in: Proceedings of the National Academy of Sciences - PNAS 1992-02, Vol.89 (3), p.1085-1089
• Main Authors: Coe, J.E. (National Institutes of Health, Hamilton, MT), Ishak, K.G, Ward, J.M, Ross, M.J
• Format: Article
• Language: English
• Subjects: ALIMENTOS; ANABOLICOS; ANABOLISANT; Animals; Bilirubin - blood; Biochemistry; Biological and medical sciences; Cancer; Carcinogenesis; Carcinogenesis, carcinogens and anticarcinogens; Chemical agents; CONTAMINACION; CONTAMINATION; CONTROL DE ENFERMEDADES; CONTROLE DE MALADIES; Cricetinae; Cricetulus; Dose-Response Relationship, Drug; Estrogens; Estrogens - toxicity; Female; Female animals; FOIE; Food Contamination; Food contamination & poisoning; Hamsters; Hepatocellular carcinoma; HIGADO; Histology; Hyperbilirubinemia; Lesions; Liver; Liver Neoplasms - chemically induced; Liver Neoplasms - pathology; Male; Male animals; Medical sciences; MOHO; MOISISSURE; NEOPLASMAS; NEOPLASME; PRODUIT ALIMENTAIRE; RODENTIA; Rodents; Tamoxifen - pharmacology; Tumors; Zeranol - antagonists & inhibitors; Zeranol - toxicity
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.89.3.1085

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 initiated tumorigenesis