Carcinogenesis, Vol 19, 2151-2158, Copyright © 1998 by Oxford University Press
WA Fritz, L Coward, J Wang and CA Lamartiniere
Asian women consuming a traditional diet high in soy have a low incidence
of breast cancer, yet when they emigrate to the USA the second but not the
first generation lose this protection. Accordingly, we hypothesized that
early exposure to genistein, a major component of soy, could have a
permanent protective effect against breast cancer. Sprague-Dawley CD rats
were exposed to genistein from conception to day 21 post-partum in the diet
at concentrations of 0, 25 and 250 mg genistein/kg AIN-76A diet. At day 50
post-partum, all animals were treated with 80 mg
dimethylbenz[a]anthracene/kg body wt to induce mammary cancers. Dietary
genistein resulted in dose-dependent protection against development of
mammary tumors (fewer tumors per rat). Analysis of mammary whole mounts
showed that 21- and 50-day-old female rats had fewer terminal end buds,
terminal ductal structures that were undifferentiated and were most
susceptible to carcinogenesis. Bromodeoxyuridine incorporation studies
revealed that dietary perinatal genistein resulted in a smaller
proliferative compartment for terminal end buds. In rats fed the high
genistein dose (250 mg/kg diet) total genistein concentrations in the serum
and milk of dams 7 days postpartum were 418+/-198 and 137 pmol/ml,
respectively. Total genistein concentrations in stomach milk, serum and
mammary glands of 7- day-old offspring were 4439+/-1109 and 726 pmol/ml and
440+/-129 pmol/g, respectively. Total genistein concentrations in the serum
and mammary glands of 21-day-old offspring were 1810+/-135 pmol/ml and
370+/-36 pmol/g, respectively. Dietary perinatal genistein did not cause
significant toxicity in F0 and F1 females. We conclude that genistein in
the diet at 'physiological levels' enhances cell differentiation, resulting
in programming of mammary gland cells for reduced susceptibility to mammary
cancer, with no observed toxicity to the reproductive tract of F1 females.
ARTICLES
Dietary genistein: perinatal mammary cancer prevention, bioavailability and toxicity testing in the rat
Department of Pharmacology and Toxicology and UAB Comprehensive Cancer Center, University of Alabama at Birmingham, 35294-0019, USA.
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C. A Lamartiniere Protection against breast cancer with genistein: a component of soy Am. J. Clinical Nutrition, June 1, 2000; 71(6): 1705S - 1707. [Abstract] [Full Text] [PDF]
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T. Ohta, S. Nakatsugi, K. Watanabe, T. Kawamori, F. Ishikawa, M. Morotomi, S. Sugie, T. Toda, T. Sugimura, and K. Wakabayashi Inhibitory effects of Bifidobacterium-fermented soy milk on 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine-induced rat mammary carcinogenesis, with a partial contribution of its component isoflavones Carcinogenesis, May 1, 2000; 21(5): 937 - 941. [Abstract] [Full Text] [PDF]
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