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Eepidemiologic studies show consistently that consumption of fruits and vegetables protects against many cancers(1). However, the phytochemicals accounting for this effect have not been identified since the cancer preventive activity of vegetarian food groups is much stronger compared to that of commonly studied micronutrients. Due to the suggested anti cancer activity and due to the high dietary exposure to humans(0.2-1.0g daily) dietary flavonoids and isoflavonoids are considered to be promising candidates as dietary cancer preventive agents(1,2). Isoflavonoids deserve particular attention in this respect because they occur in very large amounts in soy foods(3-5) which are consumed in populations in Asia with low rates of certain cancers. Epidemiologic studies concerned with the assessment of the role of isoflavonoids in health and disease require fast, reliable and affordable techniques to measure the anticancer potency and levels of these phytochemicals in humans favorably through non-invasive protocols. We investigated the effects of the effects of the predominant dietary flavonoids and isoflavonoids at inhibiting neoplastic transformation induced by 3-methylcholanthrene in C3H 10T1/2 murine fibroblasts(6). Most phenolic agents tested were found to be equal to or superior to carotenoids or vitamins in effectiveness. Some flavonoids tested showed complete inhibition of transformation when applied at 1.0 ㎛ which are physiological levels reached after a usual vegetarian meal. Structure-activity comparison among the compounds tested revealed that flavonoids with a vicinal diphenol structure in ring ’B’ exhibited the strongest anti cancer potency in a dose dependent manner. Interestingly, flavonoids and isoflavonoids showed a greater inhibition of transformation when applied in combination as occurring in foods which suggests synergistic mechanism of action. HPLC analysis established in our laboratory revealed 3 μmol/h, 2m and 0.2 ㎛ of total isoflavones (daidzein, genistein and glycitein) in urine(3), plasma(4) and breast milk(7), respectively, after intake of 20g soybeans. Isoflavones were found to be abdorbed into blood very fast and showed a biphasic pattern with peak levels observed 1-2 hours and 8-12 hours after soy intake(8). This may be due to unconjugated isoflavones in soy foods being available for immediate uptake. In contrast 90% of isoflavones in soy are present as glucosides which require bacterial hydrolysis in the gut prior to absorption(9). Elimination from the blood stream was observed to be accomplished 36-48 hours after soy exposure, mostly through renal excretion(10) and partly through the bile(11). Interestingly, we observed a 10 times lower elimination pattern in renal end disease patients compared to healthy individuals(12) due to the blocked primary elimination pathway through the kidney and due to the fact that dialysis did not remove circulating isoflavonoids. Therefore, renal end disease patients were identified to experience extremely high isoflavonoid exposure upon soy consumption which requires further investigation regarding biological effects. Total urinary isoflavonoid excretion was found to correlate very well with dietary intake of soy products as assessed by dietary recalls of food frequency questionnaires in 102 women and 50 men and women of various ethnicity from Hawaii(13), in 147 Chinese from Singapore(14), and 60 women from Shanghai(15). This suggests that isoflavones can be used as a reliable biomarker for soy exposure in future epidemiologic studies assessing the role of soy or isoflavones regarding cancer protective potency. In a case control study with 120 women from Shanghai we observed a protective effect of dietary isoflavones and to a lesser extent, of dietary lignans against breast cancer(16). Women in the tertile of highest urinary isoflavone excretion as well as women in the middle tertile experience a 50% decrease in risk to develop breast cancer versus those in the tertile with lowest isoflavone excretion. These findings support a potential breast cancer effect achieved by soy consumption in populations that eat soy foods habitually.
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