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Dietary Restriction and Toremifene on PhIP induced Carcinogenesis in rats
Author(s) -
CaneneAdams Kirstie,
Sfanos Karen S.,
De Marzo Angelo M.
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.863.7
Subject(s) - toremifene , prostate , prostate cancer , endocrinology , medicine , carcinogen , estrogen receptor , seminal vesicle , chemistry , estrogen , cancer , breast cancer , tamoxifen , biochemistry
Toremifene inhibits estrogen receptor (ER) alpha which is found in prostate stroma and epithelium, recurring prostate cancer, and metastasis. Exposure to 2‐amino‐1‐methyl‐6‐phenylimidazo[4,5‐b]pyridine (PhIP), the cooked meat heterocyclic amine, results in binding to ER alpha and cancer. Our hypothesis is the estrogenic effects of PhIP are responsible for carcinogenicity and blocking ERα via toremifene would prevent the effects of PhIP. We provided PhIP (70mg/kg) with or without toremifene (~8.6 mg/kg) in AIN93G diets to male Fischer rats for 20 weeks and then AIN93G diet for 32 weeks before collecting prostates, seminal vesicles, testes, skin, and intestines. Toremifene + PhIP rats consumed 37% less calories than PhIP rats thus a 37% dietary restricted (DR) + PhIP group was used as a control. Decreases in prostate and seminal vesicle weights, histological changes, and lack of mature sperm in the testes’ tubules were seen with toremifene. Ventral prostates showed decreased androgen receptor levels with toremifene, while testes showed no positivity. CK5 increased with toremifene, whereas PhIP had the opposite effect. PhIP rats had the greatest incidences of skin, intestinal, and prostate carcinomas. While some reductions were seen with DR the greatest effects were in rats given toremifene. We conclude that in the rat toremifene has marked anti‐androgenic and anticancer effects.