Chemoprevention of DMBA-induced mammary cancer in rats by dietary soy

Abstract

This study was designed to assess the potential chemopreventive effect of the administration of a standardized soy extract, SOYSELECT, on 7,12-Dimethylbenz[a]anthracene (DMBA)-induced mammary tumors in rats. Three groups, 24 females each, were used. Animals were fed either a phytoestrogen-free diet alone (control) or the same diet supplemented with 0.35% or 0.7% of soy extract. Treatment started at weaning and continued to the end of the study (24 weeks after DMBA administration). At day 50 of age all animals received via oral gavage 80 mg/kg DMBA. Only tumors subsequently classified as adenocarcinomas were considered for data evaluation. In rats on the soy diet, mammary tumors took a longer period of time to develop as compared to control rats. However, at the end of the study, no relevant difference in tumor incidence and multiplicity was observed among the groups. The most significant changes were seen between control and soy-treated groups when tumor dimension and results from histopathologic examination were considered. The latter, in fact, showed a dose-dependent reduction in the percentage of poorly differentiated tumors in treated animals. This change was statistically significant in animals receiving 0.7% soy. In addition, assessment of estrogen and progesterone receptor (ERalpha, PR) levels, revealed a significant reduction in the percentage of ERalpha and PR positive tumors in animals receiving 0.7% dietary soy, when compared to controls. Interestingly, genistein and daidzein plasma levels determined at the end of the study were within the range of those detected in people consuming large amounts of soyfoods.

Phytoestrogens

“…In contrast to the results of these studies, dietary feeding of supraphysiological concentrations of daidzein to female rats neither caused significant toxicity to the reproductive tract nor provided protection against chemically induced mammary cancer (107). In studies in which rats were fed a standardized soy extract instead of pure isoflavone, chemically induced mammary adenocarcinomas took longer to develop than in control animals, but at the end of the study no difference in tumor multiplicity or incidence was observed between treatment and controls (62).…”

The role of early life genistein exposures in modifying breast cancer risk

“…Only one of the five studies that exposed rats to genistein or SPI found any effect on mammary tumour incidence or multiplicity (Constantinou et al, 2001), and two studies reported a longer tumour latency (Constantinou et al, 2001;Gallo et al, 2001). The study of Constantinou et al (2001) found that an exposure to SPI that was depleted of IFs had the most significant effect on tumour latency and multiplicity.…”

Effects of high-isoflavone soy diet vs. casein protein diet and obesity on DMBA-induced mammary tumor development

“…On the other hand, in a large cohort study of British women no effects of dietary isoflavone intake and breast cancer risk were found among either pre-or post-menopausal women (10). Experimental studies showed variable results on breast cancer reduction by soy or the soy isoflavone genistein (11)(12)(13)(14)(15). For example, it was reported that genistein reduces the growth of tumors that arise from inoculated human or mouse breast cancer carcinoma cells in pre-menopausal mouse models (16,17).…”