The isoflavone genistein has been shown to stimulate the growth of existing mammary tumors in ovariectomized athymic mice implanted with estrogen-sensitive human breast cancer cells. However, these results contrast with the human research in that clinical studies show that isoflavone exposure has no impact on markers of breast cancer risk and prospective epidemiologic studies show post-diagnosis soy intake reduces recurrence and improves survival. Furthermore, it has been established that rodents metabolize isoflavones differently than humans which raises questions about the utility of using rodents for evaluating isoflavones.
This study from the Netherlands provides additional data showing rodent and human isoflavone metabolism differs. The Dutch researchers found that under similar experimental conditions, rat breast tissue S9 fraction was about 30 times more potent in deconjugating isoflavone glucuronides to their respective aglycones than was the human breast tissue S9 fraction. The S9 fraction refers to the supernatant fraction obtained from an organ homogenate by centrifuging at 9000 g for 20 minutes in a suitable medium; this fraction contains cytosol and microsomes. The microsome component of the S9 fraction contains cytochrome P450 isoforms (phase I metabolism) and other enzyme activities. The cytosolic portion contains the major part of the activities of transferases (phase II metabolism).
The finding that in comparison to the human breast tissue, rat breast tissue more effectively deconjugates isoflavone glucuronides is extremely important because only when isoflavones are in their aglycone form are they able to bind to estrogen receptors and exert estrogen-like effects. Upon absorption, isoflavones are conjugated primarily with glucuronic acid in the liver and intestine. Consequently, about 98% of the isoflavones in the circulation are conjugated and mostly biologically inactive. However, as this research shows, the mammary gland of the rat very efficiently deconjugates the glucuronide thereby producing an active form of isoflavones. Therefore, using rodents to study isoflavones can lead to erroneous conclusions about the effects of these soybean constituents in humans.
Islam MA, Bekele R, Vanden Berg JH, et al. Deconjugation of soy isoflavone glucuronides needed for estrogenic activity. Toxicol In Vitro. (2015).