Genistein Alters the Ontogeny of Mammary Gland Development and Protects Against Chemically-Induced Mammary Cancer in Rats

Lamartiniere, Coral A.; Murrill, W. B.; Manzolillo, P. A.; Zhang, J.-X.; Barnes, Stephanie L.; Zhang, Xueshu; Wei, Huachen; Brown, Nesbitt D.

doi:10.3181/00379727-217-44245

Cited by 132 publications

(75 citation statements)

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“…By comparison, the levels of phytoestrogens in infants fed cow's milk or breastmilk (from a woman consuming a typical Western diet ) are negligible. These large phytoestrogen exposures may be beneficial ( Lamartiniere et al, 1998 ) , but more research on exposure in children is needed. Specifically, our future research interest focuses on the ability of dietary phytoestrogens to mitigate the effects of environmental estrogen exposure in children.…”

Section: Discussionmentioning

confidence: 99%

HPLC-MS/MS method for the measurement of seven phytoestrogens in human serum and urine

Valentín-Blasini

Blount

Rogers

et al. 2000

J Expo Sci Environ Epidemiol

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The elevated exposure of children to hormonally active dietary phytoestrogens has led to the need for rapid, sensitive, and precise assays for phytoestrogen metabolites in physiological matrices. Here we report the development of a high -performance liquid chromatography ( HPLC ) MS / MS method for the quantitative detection of seven phytoestrogens in human serum and urine. The method uses enzymatic deconjugation of the phytoestrogen metabolites followed by solid phase extraction ( SPE ) and reverse -phase HPLC. The phytoestrogens are detected using a Sciex API III heated nebulizer atmospheric pressure chemical ionization ( HN -APCI ) interface coupled with tandem mass spectrometry. This method allows the detection of the primary dietary phytoestrogens ( isoflavones and lignans ) in human serum and urine with limits of detection ( LODs ) in the low parts per billion range. The combination of tandem mass spectrometry and chromatographic separation of the analytes helps ensure the selectivity of the method. Stable isotope -labeled internal standards for all seven analytes improve the precision of the assay, resulting in interday CV values of < 10% for most compounds studied. The accuracy and precision of the method were monitored over time using quality control ( QC ) samples containing known amounts of phytoestrogens. The majority of phytoestrogens in human sera and urine are present as their glucuronide and sulfate conjugates. Therefore, the thoroughness of deconjugation for each sample was monitored by the addition of a conjugated internal standard and subsequent detection of deconjugated compound. This method proves to be efficacious for measuring baseline urinary phytoestrogen levels in the American population and should prove useful for assessing the modulatory effects of dietary phytoestrogens on endocrine disrupter action in children.

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Section: Discussionmentioning

confidence: 99%

HPLC-MS/MS method for the measurement of seven phytoestrogens in human serum and urine

Valentín-Blasini

Blount

Rogers

et al. 2000

J Expo Sci Environ Epidemiol

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“…The effect is an increase in the latency period for tumor appearance and a decrease in tumor burden. Apparently direct actions of isoflavones on breast morphology caused increased differentiation of the terminal end-buds to lobules (Lamartiniere et al, 1998a). Additionally phytoestrogens have been shown to modulate epidermal growth factor (EGF) and the EGF-receptor; an effect which may have implications in tumor development (Brown et al, 1998).…”

Section: Discussionmentioning

confidence: 99%

Animal Models Impacted by Phytoestrogens in Commercial Chow: Implications for Pathways Influenced by Hormones

Brown

Setchell

2001

Laboratory Investigation

267

235

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SUMMARY:It is generally not known that most commercial rodent diets are formulated with soy protein and deliver large daily doses of isoflavones to animals throughout their lifespan, including the in utero period. Here, we demonstrate that isoflavones are bioavailable and show that commercial rodent diets universally used by animal facilities lead to very high steady-state serum isoflavone concentrations in adult rats (2613 Ϯ 873 ng/mL) and mice (2338 Ϯ 531 ng/mL), exceeding the animal's endogenous estrogen level by 30,000-to 60,000-fold. We demonstrate the maternal-fetal intrauterine transfer of isoflavones in animals fed a standard Purina 5001 soy-containing diet and show that newborn rat pups have high serum isoflavones levels (540 Ϯ 174 ng/mL) that are maintained throughout the suckling period by passage of isoflavones into maternal milk. These findings have profound implications for all animal experiments, including multigenerational studies and studies of transgenic animals, especially if biochemical or morphological end-points are influenced by the hormonal or nonhormonal properties of phytoestrogens. These compounds have the potential to modulate genotypic and phenotypic expression in general, and therefore, all investigators should be vigilant to the phytoestrogen composition of commercial rodent diets because there is a history of potent biological effects in larger animals and in humans from high circulating isoflavone concentrations. (Lab Invest 2001, 81:735-747).A lthough phytoestrogens are ubiquitous in the plant kingdom, it is soybeans and foods made with purified soy proteins that are by far the greatest contributors of isoflavones to animal and human diets (Coward et

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“…The effect of DAI was delayed compared with that of GEN. No significant changes in protein tyrosine kinasemediated phosphorylation or topoisomerase II activity were observed in the mammary gland or mammary tumors, even with higher isoflavone doses (40 mg/kg/day), suggesting that the observed chemoprevention was mediated via other mechanisms (109). Threeday sc treatments with a much higher GEN dose (500 mg/kg/day) during the neonatal (110) or prepubertal period (97) resulted in more marked reductions (50%) in tumor number in DMBA-treated rats.…”

Section: Proliferation Of Breast Epitheliummentioning

confidence: 99%

“…Neonatal or prepubertal doses of 500 mg/kg/day GEN significantly reduced the number of terminal end buds and cell proliferation indices at 50 days of age (97,110). Transforming growth factor (TGF)-α and epidermal growth factor (EGF) receptor were upregulated in terminal duct structures immediately after treatment, but the EGF signaling pathway was downregulated by 50 days of age (122).…”

mentioning

confidence: 97%

Cross-species and interassay comparisons of phytoestrogen action.

Whitten

Patisaul

2001

Environ Health Perspect

171

104

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This paper compiles animal and human data on the biologic effects and exposure levels of phytoestrogens in order to identify areas of research in which direct species comparisons can be made. In vitro and in vivo assays of phytoestrogen action and potency are reviewed and compared to actions, dose-response relationships, and estimates of exposure in human subjects. Binding studies show that the isoflavonoid phytoestrogens are high-affinity ligands for estrogen receptors (ERs), especially ER beta, but have lower potency in whole-cell assays, perhaps because of interactions with binding proteins. Many other enzymatic actions require concentrations higher than those normally seen in plasma. In vivo data show that phytoestrogens have a wide range of biologic effects at doses and plasma concentrations seen with normal human diets. Significant in vivoresponses have been observed in animal and human tests for bone, breast, ovary, pituitary, vasculature, prostate, and serum lipids. The doses reported to be biologically active in humans (0.4--10 mg/kg body weight/day) are lower than the doses generally reported to be active in rodents (10--100 mg/kg body weight/day), although some studies have reported rodent responses at lower doses. However, available estimates of bioavailability and peak plasma levels in rodents and humans are more similar. Steroidogenesis and the hypothalamic-pituitary-gonadal axis appear to be important loci of phytoestrogen actions, but these inferences must be tentative because good dose-response data are not available for many end points. The similarity of reported proliferative and antiproliferative doses illustrates the need for fuller examination of dose-response relationships and multiple end points in assessing phytoestrogen actions.

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Genistein Alters the Ontogeny of Mammary Gland Development and Protects Against Chemically-Induced Mammary Cancer in Rats

Cited by 132 publications

References 0 publications

HPLC-MS/MS method for the measurement of seven phytoestrogens in human serum and urine

HPLC-MS/MS method for the measurement of seven phytoestrogens in human serum and urine

Animal Models Impacted by Phytoestrogens in Commercial Chow: Implications for Pathways Influenced by Hormones

Cross-species and interassay comparisons of phytoestrogen action.

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