Journal Article

MOLECULAR EPIDEMIOLOGY AND CANCER PREVENTION: Prepubertal genistein exposure suppresses mammary cancer and enhances gland differentiation in rats

W.Britton Murrill, Nadine M. Brown, Jun-Xuan Zhang, Patricia A. Manzolillo, Stephen Barnes and Coral A. Lamartiniere

in Carcinogenesis

Volume 17, issue 7, pages 1451-1457
Published in print July 1996 | ISSN: 0143-3334
e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/17.7.1451
MOLECULAR EPIDEMIOLOGY AND CANCER PREVENTION: Prepubertal genistein exposure suppresses mammary cancer and enhances gland differentiation in rats

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Genistein, a component of soy, was administered to pre-pubertal female Sprague-Dawley CD rats and investigated for chemoprevention against mammary cancer. Genistein, at 500 μg/g body wt or an equivalent volume of the vehicle, dimethylsulfoxide (DMSO), was injected (s.c) on days 16, 18 and 20 post-partum. At day 50 post-partum all animals were exposed to 80 μg dimethylbenz[a]anthracene (DMBA) per g body wt. Animals treated prepubertally with genistein as compared to DMSO had reduced incidence and significantly fewer adenocarcinomas per animal. Mammary whole mount analysis showed that prepubertal genistein treatment resulted in mammary glands of 50-day-old rats developing fewer terminal end buds and more lobules II. Cell proliferation studies with bromodeoxyuridine (BrdU) showed that terminal end buds from mammary glands of 50-day-old females treated prepubertally with genistein had significantly fewer cells in S-phase of the cell cycle. Serum genistein concentrations in 21- and 50-day-old females following prepubertal genistein treatment were 4.2 ± 0.6 μM and 102 ± 30 nM, respectively. Animals treated prepubertally with genistein as compared to vehicle spent more time in the estras phase of the estrus cycle, although all animals did cycle. In 50-day-old females, circulating estradiol-17β and progesterone concentrations were not significantly altered by the prepubertal genistein treatment Oocyte/follicle counts and numbers of atretic follicles and corpora lutea were not significantly different between the genistein- and vehicle-treated animals. We conclude that genistein treatment during the prepubertal period can suppress the development of chemically-induced mammary cancer without significant toxicity to the endocrine/reproductive system.

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Subjects: Clinical Cytogenetics and Molecular Genetics

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