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1.
Isoflavone extracts of red clover Trifolium pratense L. (cv. Pawera) with dissimilar glucoside conjugate profiles were obtained by employing different postharvest drying methods. The most prominent isoflavones found were formononetin and biochanin A and their corresponding glucosides and malonyl glucoside esters. Postharvest freeze drying inhibited the conversion of the glycosides to the aglycones, while vacuum drying allowed for maximum conversion of the glycosides to their corresponding aglycones. Air drying produced a low level of the aglycones formononetin and biochanin A, and oven drying promoted decarboxylation of the malonyl glucosides to the acetyl glucosides. Exposure to enhanced UV-B radiation resulted in an increase in total formononetin and biochanin A isoflavone levels, indicating that harvest during a period of high ambient UV-B radiation may be appropriate for maximum yield. The levels of caffeic acid and flavonols also increased by about 40 and 250%, respectively, on exposure to enhanced UV-B radiation.  相似文献   

2.
Native beta-glucosidase activity in soy bread can convert isoflavone glucosides to aglycones during proofing, and this study determined the time-temperature dependence of this process. Samples were taken every hour for 4 h during proofing at 22, 32, and 48 degrees C to determine beta-glucosidase activity and isoflavone profiles of the dough. After 1-2 h, the beta-glucosidase activity increased 43-84% achieving a plateau value at 22 degrees C but declining when proofed beyond 2 h at 32 degrees C and 48 degrees C. Large increases in aglycones and corresponding decreases in the simple glucosides were observed during proofing. The level of malonyl-glucosides decreased 3-15%, and acetyl-glucosides were fairly constant. The two higher temperatures drove more rapid conversion: 70-73% of simple glucosides in 2-4 h. The extent of conversion in the early proofing periods corresponded to beta-glucosidase activity. The optimum time-temperature protocol was 2 h at 48 degrees C resulting in a rapid, high conversion.  相似文献   

3.
LC/UV/ESI-MS analysis of isoflavones in Edamame and Tofu soybeans   总被引：2，自引：0，他引：2  
High-performance liquid chromatography coupled with ultraviolet and electrospray ionization mass spectrometry (HPLC/UV/ESI-MSD) was applied to the study of isoflavones in both Edamame and Tofu soy varieties, from which the immature fresh soybeans or the mature soybean seeds are consumed, respectively. Positive atmospheric pressure interface (API) MS and MS/MS were used to provide molecular mass information and led to the identification of a total 16 isoflavones, including three aglycones, three glycosides, two glycoside acetates, and eight glycoside malonates. The major isoflavones in soybean seeds were daidzein and genistein glycoside and their malonate conjugates. Trace levels of daidzein and genistein acetyl glycosides were found only in the mature dry soybean seeds. To facilitate quantitative analysis, acid hydrolysis during extraction of soy samples was selected to convert the various phytoestrogen conjugates into their respective isoflavone aglycones, allowing accurate quantitation of total phytoestrogens as aglycones. On the basis of HPLC combined with UV and MS detection, all three targeted soy isoflavone aglycones, daidzein, genistein and glycitein in hydrolyzed extracts were successfully quantified within 25 min with formononetin used as the internal standard. The standard curves of UV detection were fitted in the range of 14.16-29000 ng/mL for daidzein, 15.38-31500 ng/mL for genistein, and 11.72-24000 ng/mL for glycitein. For MS detection, the standard curves were established in the range of 3.54-1812.5 ng/mL for daidzein, 3.85-1968.75 ng/mL for genistein, and 2.93-1500 ng/mL for glycitein. Good linearities (r(2) > 0.999 for UV and r(2) > 0.99 for MS) for standard curves were achieved for each isoflavone. The accuracy and precision (RSD) were within 10% for UV detection and 15% for MS detection (n = 10). Using this method, the phytoestrogen levels of total isoflavone aglycones from 30 soybean seed varieties were then evaluated for confirmation of the technique. Total isoflavones ranged across the varieties from 0.02 to 0.12% in the Edamame varieties, which are harvested while the seeds are still immature, and from 0.16 to 0.25% in Tofu varieties, harvested when the seeds are physiologically mature. While the literature has focused on the isoflavone content of soy products and processing soy, this report provides a reliable analytical technique for screening of authenticated fresh immature Edamame soybeans and Tofu soybeans.  相似文献   

4.
A soybean angiotensin I converting enzyme (ACE) inhibitory peptide fraction was reported to have antihypertensive activity in a rat study. The purpose of the present study was to examine if the presence of isoflavones in the soybean ACE inhibitory peptide fraction may contribute to the blood-pressure-lowering property. The isoflavone concentration in soybean samples was analyzed on a C 18 reverse-phase column using a two-step gradient solvent system. Producing soybean hydrolysate led to a nearly 40% loss of isoflavones compared with the original soybean flour, but the isoflavone composition did not change and the dominant isoflavone chemicals remained as 6'-O-malonylgenistin and 6'-O-malonyldaidzin. Ion exchange chromatography affected significantly both the content and the composition of the isoflavones. The dominant isoflavones in the ion-exchanged fraction were aglycones and nonacylated isoflavones, accounting for 95.8% of the total amount of 987.7 microg/g. It was calculated that the isoflavone content in the soybean ACE inhibitory peptide fraction was 25 times less than the minimal effective isoflavone dose reported. In vitro study also showed that adding isoflavones into both soybean flour hydrolysate and soybean ACE inhibitory peptide samples to a concentration of as high as 31.5% (w/w) did not affect ACE inhibitory activity (IC 50 values). The findings along with previously published results indicated that the contribution of isoflavones in soybean ACE inhibitory peptide fraction to the blood-pressure-lowering property in a short-term feeding study might be negligible.  相似文献   

5.
Bread made partially with soy may represent a viable alternative for increasing soy consumption in populations consuming Western diets. The potential health‐promoting activity of soy isoflavones may depend on their abundance and chemical form. The objective of this study was to characterize the changes in isoflavone distribution and β‐glucosidase activity during the soy breadmaking process. Soy bread ingredients were combined and mixed to form a dough that was subsequently proofed at 48°C for 1–4 hr and baked at 165°C for 50 min to produce breads. The isoflavone composition and β‐glucosidase activity in bread ingredients, doughs, and breads were monitored. Soy ingredients and wheat flour (not bread yeast) were the major contributors of the β‐glucosidase activity in bread. No degradation of isoflavones was observed during breadmaking but the isoflavone distribution was largely altered. Proofing and baking have important but different roles in changing the isoflavone distribution. Proofing converted isoflavone β‐glucosides to aglycones by highly specific β‐glucosidase activity. Thermal treatment during baking significantly decreased the isoflavone malonylglucosides and increased isoflavone β‐glucosides. Enzyme activity during proofing and the balance between formation and deconjugation of isoflavones during baking determine the isoflavone content and composition in the final product.  相似文献   

6.
Soybean isoflavones have multiple beneficial health effects especially on estrogen-deficient diseases such as menopausal symptoms. In this study, isoflavones were produced from soybean flour, and the extraction and purification parameters were optimized to give a high yield of total isoflavones, about 0.62 mg of aglycones/g of soybean flour, which is >2 times the initial yield. HPLC analysis and MTT cell proliferation assay using MCF-7 cells revealed that the product thus obtained not only contained a high content of isoflavone aglycones but also had estrogenic activity. MTT data also revealed that both genistein and daidzein exhibited estrogenic effects at lower concentrations and antiproliferative effects at higher concentrations, and 1 microM genistein and 10 microM daidzein exerted significant estrogenic activities, which were not more than that of the endogenous level of 17beta-estradiol (E2). The production method developed can be used as a guideline for manufacturing soy isoflavones, and the MTT assay was demonstrated to be suitable for quality control on isoflavone products. The results on the estrogenic properties of isoflavones can be used as reference data for their effective and safe usages in estrogenic therapy.  相似文献   

7.
An efficient analytical method utilizing high-performance liquid chromatography (HPLC)/evaporative light scattering detector (ELSD) was developed to isolate and quantify the two major soyasaponin aglycones or precursors in soybeans, triterpene soyasapogenol A and B. Soaking of seeds in water up to 15 h did not change the content of soyasapogenols. Seed germination had no influence on soyasapogenol A content but increased the accumulation of soyasapogenol B. Soyasapogenols were mainly concentrated in the axis of the seeds as compared with the cotyledons and seed coat. In the seedling, the root (radicle) contained the highest concentration of soyasapogenol A, while the plumule had the greatest amounts of soyasapogenol B. In 10 advanced food-grade soybean cultivars grown in four locations in Ontario, total soyasapogenol content in soybeans was 2 +/- 0.3 mg/g. Soyasapogenol B content (1.5 +/- 0.27 mg/g) was 2.5-4.5-fold higher than soyasapogenol A content (0.49 +/- 0.1 mg/g). A significant variation in soyasapogenol content was observed among cultivars and growing locations. There was no significant correlation between the content of soyasapogenols and the total isoflavone aglycones.  相似文献   

8.
A combination of analytical techniques was used to examine and quantify seed compositional components such as protein, lipid, free sugars, isoflavones, and soyasaponins during soybean development and maturation in two Korean soybean cultivars. Protein accumulation was rapid during reproductive stages, while lipid content was only relatively moderately increased. The major carbohydrate saccarides sucrose and stachyose constantly increased during the reproductive stage. Previously published results suggest that the free sugar and lipid content reached their maximal concentrations at a relatively early stage of seed development and remain constant in comparison to other chemical components. The malonylglucosides were the predominant isoflavone form followed by the glucosides, acetyl glucosides, and aglycone forms. As soybean seed matures, total soyasaponin concentration was constantly decreased until the R8 stage. Soyasaponin beta(g) was the major soyasaponin in DDMP-conjugated group B soyasaponins, followed by the non-DDMP counterpart soyasaponin I and soyasaponin A1. The ratio of total isoflavone to total soyasaponin in the developing soybean increased from 0.06 to 1.31. Protein, lipid, and free sugar contents in the developing soybean seeds showed significant positive correlations with conjugated isoflavones and total isoflavone concentration, while the lipid contents showed a negative correlation with the isoflavone aglycone. Protein, lipid, and free sugar contents showed a negative correlation with total group A and B soyasaponins and total soyasaponins; however, only the soyasaponin A content was significantly negatively correlated with free sugar content. Total soyasaponin content was negatively correlated with isoflavone content (r = -0.828 at p < 0.01).  相似文献   

9.
Soybean [Glycine max (L.) Merr.] is a rich source of isoflavones that are often affected by biotic and abiotic factors. The objectives of this study were to evaluate the effect of various concentrations of three natural elicitors applied at different soybean growth stages on isoflavone content and to compare the efficiency of several solvent systems in isoflavone extraction and quantification. The isoflavones extracted from R96-3444 soybean using eight solvent systems were separated, identified, and quantified by a high-performance liquid chromatography (HPLC) procedure. The soybean plants were sprayed with salicylic acid, methyl salicylate, or ethyl acetate at 0, 10(-6), 10(-3), and 10(-1) M at R1 (blooming) or R4 (full pods) growth stage. Results showed that 10(-3) M ethyl acetate sprayed at the R1 stage significantly increased total isoflavone content and the levels of some individual isoflavones in soybean seeds. With all the elicitors that were tested, concentration was a more important factor than application time with respect to isoflavone content with lower concentrations being more effective on most isoflavones. A 53% acetonitrile solvent system was the best solvent system for extracting total isoflavone, malonyl glucosides, genistein, glycitin, genistin, acetyl-daidzin, and acetyl-genistin. The results of this study will be useful for increasing the isoflavone content in desirable soybean varieties and improving isoflavone concentration during extraction.  相似文献   

10.
Isoflavones in soybean were extracted in the crude form using 80% food-grade ethanol at 80 degrees C for 6 h and followed by concentration and dehydration. The soy extract contained isoflavones primarily in the forms of glucosides. In vitro antioxidant activities of the soy extract containing 20-500 ppm isoflavones were conducted using a Rancimat method. The results showed that soy isoflavone extract had strong in vitro antioxidant activity. There was a dose-dependent response for the in vitro antioxidant activity at the lower concentrations but not at the higher concentrations. In vivo antioxidant property was determined by measuring the antioxidant enzymes, superoxide dismutase, and catalase in various organs of rats that were fed with diets containing partially oxidized oil and various levels of isoflavones for up to 24 weeks. Neither short-term (8 weeks) feeding nor low isoflavone content (50 ppm) induced changes in superoxide dismutase or catalase activities in rats. Only diets containing high isoflavone contents (150 and 250 ppm) showed obvious elevated enzymatic levels in various organs. In addition, a laboratory-prepared tofu containing approximately 50 ppm isoflavones had better effects than the soy extract with the 250 ppm isoflavone group, which indicated that molecules other than isoflavones may have a synergistic effect on in vivo antioxidant enzyme inductions of tofu.  相似文献   

11.
Soy isoflavone is the generic name for the isoflavones found in soy. We determined the concentrations of 15 soy isoflavone species, including 3 succinyl glucosides, in 22 soy foods and isoflavone supplements by high-performance liquid chromatography (HPLC). The total isoflavone contents in 14 soy foods and 8 supplements ranged from 45 to 735 μg/g and from 1,304 to 90,224 μg/g, respectively. Higher amounts of succinyl glucosides were detected in natto, a typical fermented soy product in Japan; these ranged from 30 to 80 μg/g and comprised 4.1-10.9% of the total isoflavone content. In soy powder, 59 μg/g of succinyl glucosides were detected, equivalent to 4.6% of the total isoflavone content. These data suggest that the total isoflavone contents may be underestimated in the previous studies that have not included succinyl glucosides, especially for Bacillus subtilis -fermented soy food products.  相似文献   

12.
Isoflavone levels and isoflavone chemical composition in 11 cultivars of soybean, including 4 Indian and 7 genotypes of soybean grown in Bulgaria, were analyzed as determined by C 18 reversed phase high-performance liquid chromatography coupled with a photodiode array detector. Antioxidant activity of soybean extracts was assessed using the 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity, and total phenolic compounds (TPC) were determined by using Folin-Ciocalteu reagent. The range of total isoflavones (TI) was 558.2-1048.6 microg g (-1) of soy in Indian cultivars, and it was 627.9-1716.9 microg g (-1) of soy in the case of Bulgarian cultivars. The highest and lowest total isoflavone contents were observed for Maus-2 (1048.6 microg g (-1) of soy) and Hardee (558.2 microg g (-1) of soy), respectively, for the Indian cultivars, and they were observed for Boryara (1716.9 microg g (-1) of soy) and Line 5 (627.9 microg g (-1) of soy) for the Bulgarian genotypes. DPPH radical scavenging activity did not differ significantly among the cultivars and did not correlate with TI, whereas TPC correlated well with TI and weakly with DPPH. Malonylglucoside of all the aglycones, total genistein (TGin), and total daidzein (TDin) showed strong correlation with total isoflavones, whereas acetylglucoside and aglycone levels did not significantly correlate with total isoflavone. Profiling of soybean isoflavone is helpful in understanding the regulation of isoflavone biosynthesis for greater improved resistance of crops to disease and greater health benefits for humans. This comparative study of soybean cultivars grown in India and Bulgaria throws light on their composition and nutraceutical value.  相似文献   

13.
Recent studies have shown that soy isoflavone inhibits inducible nitric oxide (NO) synthase activities and is reported to have peroxynitrite scavenging ability. Consequently, we investigated whether isoflavones (daidzein and genistein) and extracts from soy-based products (miso, soymilk, tofu, soy sprout, black soybean, soybean, and yuba) would inhibit the reactive nitrogen species (RNS) effect in vitro and in vivo. In the in vitro experiments [including the protection of cellular DNA from peroxynitrite or sodium nitroprusside damage, an inhibitory effect on nitric oxide production from lipopolysaccharide (LPS)-induced RAW 264.7 cells, and nitric oxide scavenging ability], extracts from soy-based foods showed a potent antioxidant activity and an inhibiting effect on RNS activity. These effects were correlated with total isoflavone content. In the in vivo experiments, rats were given isoflavones (4.0 mg/kg bw) or soy-based product extracts (1.0 g/kg bw) orally for 1 week and were injected with vehicle H(2)O (1 mL/kg bw) or LPS (10 mg/kg bw) on the day 7. Twelve hours after treatment, the rats were killed, and blood serum was collected for analysis. The intraperitoneal administration of LPS resulted in an increase in serum nitrite, nitrate, and nitrotyrosine concentrations. These are stable metabolite end products of nitric oxide, to 4-, 16-, and 5-fold levels, (4, 10 microM and 58 +/- 14 pmol/mL), of the placebo control, respectively. Results showed that oral administration of isoflavones and extracts from soy-based products significantly decreased serum nitrite, nitrate, and nitrotyrosine levels in LPS-induced rats. This study demonstrates that soy isoflavone supplementation may inhibit RNS-induced oxidation both in vitro and in vivo.  相似文献   

14.
Bifidobacterium animalis subsp. lactis bb12 and B. longum 20099 were used to hydrolyze isoflavone glycosides (IG) to biologically active forms, which are isoflavone aglycones (IA), in soymilk (SM) prepared from soy protein isolate (SPI) and SM supplemented with 0.5% (w/v) of lactulose (SML). Supplementation of lactulose significantly ( p < 0.05) enhanced the viable counts of B. animalis subsp. lactis bb12 and B. longum 20099 up to 2.34 and 2.15 log CFU/mL, respectively. Bifidobacterium animalis subsp. lactis bb12 and B. longum 20099 utilized 3.32 and 3.75 mg/mL of lactulose at 24 h of incubation, respectively. Supplementation of lactulose also appeared to be a key factor in decreasing the pH of SML. The biotransformation of IG to IA was enhanced significantly by 6.8-17.1% and 12.8-13.5% in SML by B. animalis subsp. lactis bb12 and B. longum 20099, respectively. However, the presence of lactulose in SML showed the stimulating effect on B. longum 20099 only after 12 h of incubation. Isoflavone aglycones ranged from 69.5 to 77.1% of total isoflavone compounds in SML after incubation.  相似文献   

15.
The reliability of databases on the isoflavone composition of foods designed to estimate dietary intakes is contingent on the assumption that soy foods are consistent in their isoflavone content. To validate this, total and individual isoflavone compositions were determined by HPLC for two different soy protein isolates used in the commercial manufacture of soy foods over a 3-year period (n = 30/isolate) and 85 samples of 40 different brands of soy milks. Total isoflavone concentrations differed markedly between the soy protein isolates, varying by 200-300% over 3 years, whereas the protein content varied by only 3%. Total isoflavone content varied by up to 5-fold among different commercial soy milks and was not consistent between repeat purchases. Whole soybean milks had significantly higher isoflavone levels than those made from soy protein isolates (mean +/- SD, 63.6 +/- 21.9 mg/L, n = 43, vs 30.2 +/- 5.8 mg/L, n = 38, respectively, p < 0.0001), although some isolated soy protein-based milks were similar in content to "whole bean" varieties. The ratio of genistein to daidzein isoflavone forms was higher in isolated soy protein-based versus "whole bean" soy milks (2.72 +/- 0.24 vs 1.62 +/- 0.47, respectively, p < 0.0001), and the greatest variability in isoflavone content was observed among brands of whole bean soy milks. These studies illustrate large variability in the isoflavone content of isolated soy proteins used in food manufacture and in commercial soy milks and reinforce the need to accurately determine the isoflavone content of foods used in dietary intervention studies while exposing the limitations of food databases for estimating daily isoflavone intakes.  相似文献   

16.
Anti-inflammatory and antiproliferative activities of anthocyanidins and anthocyanin-rich black soybean seed coats were studied in HT-29 human colon adenocarcinoma cells and carcinogen-treated F344 rats, respectively. Cyanidin and delphinidin significantly inhibited cell growth at concentrations of >or=1 microM. Anthocyanidins suppressed cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) mRNAs in TPA-stimulated HT-29 cells. Both yellow and black soybean seed coat supplementation (10%, w/w) did not significantly reduce the number of aberrant crypt foci (ACF), although a modest decrease in the number of ACF was observed in animals fed soybean seed coats. The colonic COX-2 mRNA level was suppressed in rats fed both soybean seed coat diet. The plasma prostaglandin E 2 (PGE 2) level was reduced only in rats fed black soybean seed coats. No difference was observed in either colonic iNOS mRNA or plasma nitric oxide level. These results indicate that anthocyanidins are possible anti-inflammatory agents; however, further studies are required to determine required intake levels in vivo to exert antitumor effect.  相似文献   

17.
An isoflavone conjugates hydrolyzing beta-glucosidase (ICHG) from endophytic bacterium, Pseudomonas ZD-8 was purified to homogeneity by successive ammonium sulfate precipitation, gel filtration on SephadexG-100, DEAE-sephrose CL-6B and DEAE-Sephacel chromatography. The enzyme was a monomeric protein with an apparent molecular mass of 33 kDa as determined by SDS-PAGE and gel filtration. It was optimally active at pH 6.0 and 40 degrees C and had a specific activity of 1485 U mg of protein(-1) against genistin. The ICHG readily hydrolyzed rho-nitrophenyl-beta-glucoside, rho-nitrophenyl-beta-galactoside, genistin, daidzin, with Km values of 1.64, 1.87, 0.012, 0.014 mM, respectively. The ICHG showed a pronounced specificity for glucose in the 7-position of isoflavone and flavone conjugates and hydrolyzed effectively malonyl isoflavone glucosides as well as isoflavone glucosides with similar kinetics. Glucose and glucono-delta-lactone inhibited the enzyme competitively with Ki values of 84 mM and 23 mM, respectively. The enzyme did not require divalent cations for activity, and its activity was strongly inhibited by Hg2+, Ag+, rho-chloromercuribenzoate, iodoacetic acid, and N-ethylmaleimide while reducing agents such as beta-mercaptoethanol, dithiothreitol, dithioerythritol, glutathione slightly activated the enzyme.  相似文献   

18.
In dry white wines, two different forms of instability occur: (i) substantial yellow or yellow-green deposits are observed principally due to flavonol quercetin; and (ii) protein instability leads to protein casse. Polyvinyl polypyrrolidone (PVPP) is used to adsorb phenols from beverages, and bentonite is used to eliminate heat instable protein. However, in both cases, their effects are still largely unknown. This study uses a multitechnique approach to gain a better molecular understanding of the association of polyphenol aglycones with PVPP compared to that of glucosides with PVPP. The work demonstrates, that with aglycones, three forces drive complex formation: hydrophobic interaction, H bonds, and van der Waals bonds. With glucosides, the sugar moiety removes or reduces these driving forces. Thus, if the interaction between proteins and polyphenols is responsible for haze and precipitates, as is classically assumed, PVPP could prevent quercetin sedimentation.  相似文献   

19.
The objective of the present study was to determine whether concentrations of different isoflavones (puerarin, genistein, genistin, daidzein, and daidzin) in shoots and roots of five selected soybean genotypes would respond the same or differently to red (650 nm peak transmittance) and far-red (750 nm peak transmittance) light treatments given under controlled environments. Levels of isoflavones (mg g(-1) dry weight biomass) present in seeds, control roots, and shoots and 10 day light-treated seedlings (light, dark, red, and far-red wavelengths) of soybean (Glycine max) were determined by high-performance liquid chromatography analysis in comparison with known isoflavone standards. Seeds of the five soybean genotypes studied consistently stored most of their isoflavones as glucosyl conjugates (e.g., daidzin, genistin, and puerarin). For the five soybean genotypes, isoflavone levels were lower in the seeds as compared with roots plus shoots of control, time zero (first true leaf stage) seedlings. Following 10 days of the respective light treatments, we found that (i) isoflavone levels were enhanced in dark-grown plants over light-grown plants for three of the five genotypes (a new finding) and the reverse occurred for a single genotype (a typical response of legumes) and (ii) generally, far-red end of day (EOD) light treatment enhanced total isoflavone levels in roots plus shoots over red EOD light treatment. Results from the present study show that phytochrome does appear to play a role in regulating isoflavone levels in developing soybean seedlings and that this influence by red/far-red-mediated phytochrome reactions is strongly dependent on the genotypes selected for study.  相似文献   

20.
Methyleugenol (MEG) was tested for toxicity/carcinogenicity in a 2-yr carcinogenesis bioassay because of its widespread use in a variety of foods, beverages, and cosmetics as well as its structural resemblance to the known carcinogen safrole. F344/N rats and B6C3F(1) mice (50 animals/sex/dose group) were given MEG suspended in 0.5% methylcellulose by gavage at doses of 37, 75, or 150 mg/kg/day for 2 yr. Control groups (60 rats/sex and 50 mice/sex) received only the vehicle. A stop-exposure group of 60 rats/sex received 300 mg/kg/day by gavage for 53 weeks followed by the vehicle only for the remaining 52 weeks of the study. A special study group (10 animals/sex/species/dose group) were used for toxicokinetic studies. All male rats given 150 and 300 mg/kg/day died before the end of the study; survival of female rats given 150 mg/kg/day and all treated female mice was decreased. Mean body weights of treated male and female rats and mice were decreased when compared to control. Area under the curve results indicated that greater than dose proportional increases in plasma MEG occurred for male 150 and 300 mg/kg/day group rats (6 and 12 month) and male 150 mg/kg/day mice (12 month). Target organs included the liver, glandular stomach, forestomach (female rats) and kidney, mammary gland, and subcutaneous tissue (male rats). Liver neoplasms occurred in all dose groups of rats and mice and included hepatoadenoma, hepatocarcinoma, hepatocholangioma (rats only), hepatocholangiocarcinoma, and hepatoblastoma (mice only). Nonneoplastic liver lesions included eosinophilic and mixed cell foci (rats only), hypertrophy, oval cell hyperplasia, cystic degeneration (rats only), and bile duct hyperplasia. Mice also exhibited necrosis, hematopoietic cell proliferation, and hemosiderin pigmentation. Glandular stomach lesions in rats and mice included benign and malignant neuroendocrine tumors, neuroendocrine cell hyperplasia, and atrophy and in mice included glandular ectasia/chronic active inflammation. In female rats, the forestomach showed a positive trend in the incidences of squamous cell papilloma or carcinoma (combined). Male rats also exhibited kidney (renal tubule hyperplasia, nephropathy, and adenomacarcinoma), mammary gland (fibroadenoma), and subcutaneous tissue (fibroma, fibrosarcoma) lesions. Male rats also exhibited malignant mesotheliomas and splenic fibrosis. These data demonstrate that MEG is a multisite, multispecies carcinogen.  相似文献   

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