Effects of Selenium and Low Levels of Lead on Mammary Tumor Development and Growth in MMTV-infected Female Mice

Selenium (Se) has been demonstrated in previous studies to inhibit mammary tumorigenesis in C3H mice infected with the murine mammary tumorvirus, MMTV. The antitumorigenic effects of Se in this animal model of breast cancer were subsequently shown to be counteracted by Se-antagonistic elements. Lead (Pb), for example, was found to abolish the anticarcinogenic effects of Se at 5 ppm in the drinking water. The present study was undertaken to explore the effects of Pb at just 0.5 ppm in the water, i.e., at a level comparable to the concentrations of Pb that have been measured in the tap water of older homes in some communities. Groups of 30 female virgin C3H/St mice infected with MMTV maintained on Torula yeast-based diets containing either 0.15 or 0.65 ppm of yeast-based organic Se and received either deionized water or water containing 0.5 ppm Pb as the acetate over their entire postweaning lifespan. In the control group on deionized water and the 0.15 ppm Se feed, the tumor incidence was 78.6%, which is normal for this strain. Increasing the Se content of the feed to 0.65 ppm lowered the tumor incidence to 30%, demonstrating the antitumorigenic effect of Se. In the experimental groups, the Pb-exposed mice on the 0.15 ppm Se feed developed signs of chronic Pb toxicity as evidenced by diminished weight gain that persisted up to the age of 10 months, during which period the animals remained tumor-free. Thereafter, weight gains ensued to near the values of the controls, and the tumors began to develop in rapid succession until the final tumor incidence of 73.7% was reached. In the group of mice on the 0.65 ppm Se feed, the toxic effects of Pb were diminished, as evidenced by the normal weight gains during the first 10 months but with concomitant physiological inactivation of Se, causing 82.6% of the mice to develop tumors, with the first tumor to appear at the age of 5 months, 7 months earlier than in the Pb-unexposed controls. In addition, tumor growth rates in this group were greatly accelerated and the survival of the tumor-bearing animals was significantly shortened. Direct evidence for the interactions of Pb with Se were obtained by determinations of the two elements in the livers, kidneys, and hair of tumor-free and tumor-bearing mice. However, the exposure of the mice to Pb in the water also altered the levels of Zn, Cu, Fe, and Cr in the organs and tissues, more so in tumor-bearing than tumor-free animals. The present study demonstrates the need to consider the interactions of Se with other trace elements in discussions of its mechanism of anticarcinogenic action.     

Erratum to: Lead Exposure: A Contributing Cause of the Current Breast Cancer Epidemic in Nigerian Women

Breast cancer incidence in Nigerian women has significantly increased during the past three decades in parallel with the rapid industrialization of that country. This suggested that the associated widespread contamination of the soil and of the water supplies by lead (Pb) and other industrial metals was a major contributing cause. Because of its many domestic, industrial, and automotive uses, Pb is of particular concern as it has been shown to promote the development of mammary tumors in murine mammary tumor virus-infected female C3H mice at levels as low of 0.5 ppm Pb in the drinking water. Lead belongs to the group of selenium-antagonistic elements that interact with selenium (Se), abolishing its anti-carcinogenic effect. Lead on chronic, low-level exposure in addition also accelerates tumor growth rates. Higher levels of Pb were found in blood and head hair samples of newly diagnosed patients with breast cancer, all with infiltrating ductal carcinoma, the most common form of breast cancer in Nigeria, seen at Obafemi Awolowo University, than in cancer-free controls from the same area. Evidence for interactions between Pb and Se was obtained from blood, hair, and tumor biopsy tissue analyses. Furthermore, the Pb levels in hair samples of the patients were directly correlated with the volumes of their tumors, in accord with the tumor growth-promoting effects of Pb. Conversely, Se levels in hair and blood were inversely correlated with the tumor volumes, consistent with the anti-proliferative effects of Se. Several other elements, e.g., Cd, Hg, Cr, Sn, and As, were detected in the scalp hair of the patients and the controls, although at significantly lower levels than those of Pb. However, correlation calculations revealed them also to interact with Se, suggesting that only a fraction of the Se in organs and tissues is actually present in bioactive forms. In metal-exposed subjects, a state of latent Se deficiency may exist, resulting in depressed immune functions and increased cancer susceptibility. Evidence is presented to show that Pb and other metals also interact with iodine, another vitally important essential trace element believed to protect against breast cancer development. Public health programs aiming at lowering the breast cancer risk of Nigerian women thus will have to include effective measures to protect the population from exposures to Pb and other industrial metals that are presently contaminating the environment and the water supplies.     

Inhibition of the genesis of spontaneous mammary tumors in C3H mice: effects of selenium and of selenium-antagonistic elements and their possible role in human breast cancer.

The inhibitory effect of selenium on the genesis of spontaneous mammary tumors in C3H mice is statistically significant even at toxic levels of selenium (5 and 15 ppm of Se in form of selenite added to the supply water), no evidence for stimulation of tumor growth by selenium has been obtained. Arsenite lowers the tumor incidence at higher dosage (80 ppm of As in supply water) as well, but animals developing tumors under these conditions demonstrate significantly enhanced tumor growth rates. The addition of subtoxic concentrations of zinc (200 ppm in form of ZnCl2) to supply water containing 5 ppm of Se abolishes the cancer-protecting effect of selenium. The latter result is of possible importance with respect to the human breast cancer mortality experience: The calculated dietary zinc intakes of average adults in 28 countries correlate with the female age-corrected mortalities from breast cancer directly, with P less than 0.005. The zinc concentrations in whole blood from donors in different parts of the U.S.A. are also directly correlated with the female breast cancer mortalities.     

Interactive Effects of Selenium and Cadmium on Mammary Tumor Development and Growth in MMTV-Infected Female Mice. A Model Study on the Roles of Cadmium and Selenium in Human Breast Cancer

Previous studies demonstrated that the age-corrected breast cancer mortalities in different countries are inversely correlated with the per-capita dietary intakes of selenium and directly with the estimated intakes of cadmium, zinc, and chromium, suggesting that the anticarcinogenic properties of selenium are counteracted by these elements. The tumor-preventative effects of selenium and the converse effects zinc and chromium have already been confirmed experimentally in studies with female inbred C3H mice carrying murine mammary tumor virus (MMTV). Using the same model of human breast cancer, it is now demonstrated that cadmium abolishes the cancer-protecting effects of selenium. In addition, cadmium was also found to interact with zinc, copper, and chromium. At 1.4 ppm in the drinking water, cadmium caused a significant depletion of zinc in vital organs such as the liver, which is held responsible for a delay of the appearance of the mammary tumors by 4 months and their slower growth rates relative to the Cd-unexposed controls. The results of the present study are relevant to human breast cancer prevention as selenium counteracts the effects of cadmium.     

Effect of simulated American,Bulgarian, and Japanese human diets and of selenium supplementation on the incidence of virally induced mammary tumors in female mice

In attempts to simulate the effects of diet on human breast cancer development groups of female C3H mice infected with mammary tumor virus (MMTV-) were maintained on diets formulated to resemble the typical American, Bulgarian, and Japanese human diets. The incidence of mammary tumors was the highest (84%) in group of mice receiving the simulated meat- and fat-rich American diet, which was also low in selenium (Se content: 0.15 ppm). The appearance of mammary tumors was delayed in the mice maintained on the simulated Bulgarian diet, and the final tumor incidence (27%) paralleled the correspondingly lower Bulgarian breast cancer incidence. The simulated Bulgarian diet contained more Se (0.25 ppm), and was lower in fat, meat, and sugar and higher in complex carbohydrates (cereals) than the simulated American diet. In the mice fed the simulated Japanese diet, the appearance of mammary tumors was also delayed, and the tumor incidence was diminished to 47%. In this diet, fish meal was a major source of Se, which is known to have low bioavailability. Additional supplementation of the Japanese-type diet with bioavailable Se (1 ppm) lowered the tumor incidence to 10%. Based on these studies, recommendations are made for breast cancer risk reduction by dietary means.     

Selenium and selenium-antagonistic elements in nutritional cancer prevention

Selenium is an essential trace element with antioxidative, antimutagenic, antiviral and anticarcinogenic properties. There is increasing evidence that the dietary selenium intakes are sub-optimal in the populations of many countries and that human cancer mortalities would significantly decline if additional selenium was made available either through supplementation or the fortification of certain foods. An important property of selenium is its interaction with other elements that may be present in foods, the water, the workplace and the environment, e.g. As, Cu, Ni, Co, Cr, Mn, Zn, Cd, Sn, Pb, Hg, Bi, Mo, Ag, Au, etc. The sequestration of elements by selenium represents an efficient natural detoxification mechanism for some of these elements but also results in the physiological inactivation of selenium. Animal experiments confirm that the chronic exposure to low levels of these elements abolishes the cancer-protective effect of selenium. Human cancer is likewise significantly determined by the interactions of selenium with other elements, as evidenced by epidemiological, ecological and case-control studies. Cadmium, for example, is a key risk-increasing element for prostate cancer; for breast cancer, Cd, Cr, Zn are mainly contributing; for bronchial cancer (in smelter workers), Cd, As, Cr, Sb, Co, La, all these elements are in a reciprocal relationship with Se. While selenium remains the key cancer-protective trace element, the interpretation of its mode of action necessitates consideration of the effects of selenium antagonistic elements.     

Genotype × diet interactions in mice predisposed to mammary cancer: II. Tumors and metastasis

High dietary fat intake and obesity may increase the risk of susceptibility to certain forms of cancer. To study the interactions of dietary fat, obesity, and metastatic mammary cancer, we created a population of F₂ mice cosegregating obesity QTL and the MMTV-PyMT transgene. We fed the F₂ mice either a very high-fat or a matched-control-fat diet, and we measured growth, body composition, age at mammary tumor onset, tumor number and severity, and formation of pulmonary metastases. SNP genotyping across the genome facilitated analyses of QTL and QTL × diet interaction effects. Here we describe effects of diet on mammary tumor and metastases phenotypes, mapping of tumor/metastasis modifier genes, and the interaction between dietary fat levels and effects of cancer modifiers. Results demonstrate that animals fed a high-fat diet are not only more likely to experience decreased mammary cancer latency but increased tumor growth and pulmonary metastases occurrence over an equivalent time. We identified 25 modifier loci for mammary cancer and pulmonary metastasis, likely representing 13 unique loci after accounting for pleiotropy, and novel QTL × diet interactions at a majority of these loci. These findings highlight the importance of accurately modeling not only the human cancer characteristics in mice but also the environmental exposures of human populations.     

Effects of Enriched Environment on COX-2, Leptin and Eicosanoids in a Mouse Model of Breast Cancer

Cyclooxygenase-2 (COX-2) and adipokines have been implicated in breast cancer. This study investigated a possible link between COX-2 and adipokines in the development of mammary tumors. A model of environmental enrichment (EE), known to reduce tumor growth was used for a syngeneic murine model of mammary carcinoma. 3-week-old, female C57BL/6 mice were housed in standard environment (SE) or EE cages for 9 weeks and transplanted orthotopically with syngeneic EO771 adenocarcinoma cells into the right inguinal mammary fat pad. EE housing influenced mammary gland development with a decrease in COX-2 expressing cells and enhanced side-branching and advanced development of alveolar structures of the mammary gland. Tumor volume and weight were decreased in EE housed mice and were associated with a reduction in COX-2 and Ki67 levels, and an increase in caspase-3 levels. In tumors of SE mice, high COX-2 expression correlated with enhanced leptin detection. Non-tumor-bearing EE mice showed a significant increase in adiponectin levels but no change in those of leptin, F₂-isoprostanes, PGF_2α, IL-6, TNF-α, PAI-1, and MCP-1 levels. Both tumor-bearing groups (SE and EE housing) had increased resistin, IL-6, TNF-α, PAI-1 and MCP-1 levels irrespective of the different housing environment demonstrating higher inflammatory response due to the presence of the tumor. This study demonstrates that EE housing influenced normal mammary gland development and inhibited mammary tumor growth resulting in a marked decrease in intratumoral COX-2 activity and an increase in the plasma ratio of adiponectin/leptin levels.     

Elements in Lung Tissues of Patients from a High Lung Cancer Incidence Area of China

The concentrations of trace elements are closely related to tumor genesis, progression, and therapy. In order to establish the extent to which trace elements apply to lung cancer, 15 trace elements were determined in 60 lung tissue samples from residents of Xuanwei and Fuyuan, two counties with extremely high lung cancer incidences in Yunnan province, China. The results indicated that the levels of V, Fe, Zn, Cd, Ni, Cu, Se, and Pb in the lung cancer tissues were significantly different from those in benign tissues. Among the eight elements, the levels of V, Fe, Zn, and Cd in the lung cancer tissues were lower than those in the benign tissues, while those of Ni, Cu, Se, and Pb were higher. Multiple conditional logistic regression showed that among the 15 elements, Cu, Pb (β > 0, OR > 1), and Zn (β < 0, OR < 1) were closely related to the lung cancer. Cu and Pb were classified as risk factors for local lung cancer and Zn was identified as a protective factor. The results obtained will provide dietary suggestions in terms of how to reduce lung cancer risks by appropriately balancing the intakes of certain trace elements especially for individuals who are from those two counties.     

Effect of subchronic exposure to arsenic on levels of essential trace elements in mice brain and its gender difference

The interactions of toxic metals with essential metals may result in disturbances in the homeostasis of essential elements. However, there are few reports about toxic effect of arsenic (As) on the levels of essential trace elements in the central nervous system. To investigate whether subchronic exposure to As disturbs levels of main essential trace elements in the brain of mice and whether the gender difference in the response to As are altered, the concentrations of As, Iron (Fe), copper (Cu), selenium (Se), zinc (Zn) and Chromium (Cr) in the cerebrum and cerebellum of mice exposed to As subchronically were examined by inductively coupled plasma-mass spectrometry (ICP-MS). The gender difference in the changed levels of these essential trace elements was also statistically analyzed. The concentration of As was significantly higher in the cerebrum or cerebellum of mice exposed to As than that in control group (P < 0.05). It indicates that As can accumulate in brain of mice after subchronic exposure. The concentrations of Fe, Se and Cr in the cerebrum or cerebellum were significantly lower in mice exposed to As than those in control group (P < 0.05). On the contrary, the concentration of Cu in the cerebrum or cerebellum was significantly higher in mice exposed to As (P < 0.05). Our results indicate that subchronic exposure to As may decrease the levels of Fe, Se and Cr or increase the level of Cu in the brain of mice. Moreover, the significant gender difference was found relative to the effect of As on concentration of Se in cerebrum and concentrations of Cu and Se in cerebellum of mice. Therefore, more experiments are required to further understand mechanisms whereby As interacts with essential elements in brain and induces the gender difference.     

Chromium,selenium, and other trace element intakes of a selected sample of Canadian premenopausal women

Daily Cr, Se, Ag, Cs, Rb, Sb, and Sc intakes of 84 Canadian women aged 30.3±6.1 yr (mean±SD) living in a University community and consuming self-selected diets were determined by analyses of 1-d food composites collected by the subjects. Aliquots of the homogenized food composites were freeze-dried and then analyzed by instrumental neutron activation procedures following irradiation for 72h. In all cases, trace element concentrations in the food composites were non-Gaussian. Median daily intakes were: Cr, 47 μg; Se, 74 μg; Ag, 7.1 μg; Cs, 4.4 μg; Rb, 1.5 mg; Sb 2.0 μg; and Sc, 0.38 μg. Sixty percent and 24% of the subjects received daily Cr and Se intakes, respectively, below the US Food and Nutrition Board safe and adequate range. High Cr density diets were associated with a significantly higher consumption of cheese and dry legumes and nuts (p<0.05). In the high Se density diets, intakes of grain products and breakfast cereals were significantly higher (p<0.05), and intakes of potatoes, table fats, total fat, saturated fat, and oleic acid were significantly lower (p<0.05) compared to the low Se density diets. The low daily Cr intakes evident in this study may be cause for concern in view of the increasing evidence that women may be at greater risk for deficiency of Cr than men because of Cr depletion during pregnancy.     

Trace element correlations in the blood of indian women with breast cancer

Fourteen minor (Na, K, P, Fe) and trace (Br, Co, Cr, Cs, Hg, Rb, Sb, Se, Sr, Zn) elements have been determined in pre and postoperative blood samples of 10 breast-cancer-affected. Indian women and compared with controls. The study showed elevation of Cr, Hg, Fe, Rb, Sb, and Zn and lowering of Se, K, P, and Sr contents in the blood of cancer patients. Most elemental contents in pre and postoperative stages remain unaltered except Br, Co, and Sb. Statistical significance of Fe, Se, Zn, and Hg levels has been tested by box plots. Lowering of Se in blood (-54.4%) is correlated with its enhancement in cancerous breast tissue (94.7%) of various clinical stages. Se/Zn and Se/Fe ratios are lowered in the blood of cancer patients, whereas Na/K ratio is only marginally enhanced. An attempt has been made to correlate Se levels with the dietary intake and breast cancer risk vis-a-vis American and Japanese women.     

Nutritional supplements in combination with chemotherapy or targeted therapy reduces tumor progression in mice bearing triple-negative breast cancer

The potential anti-cancer properties of selenium (Se) and eicosapentaenoic acid (EPA)/docosahexaenoic acid (DHA) have been documented. However, few studies have been conducted examining anti-tumor effects of nutritional supplements (NS) containing Se and EPA/DHA in combination with anti-cancer agents, such as taxol (Tax), adriamycin (Adr), and avastin (Ava). Compared with triple-negative breast cancer (TNBC)-bearing positive control (TB) mice, a low dose of Tax, Adr, and Ava decreased tumor size and the incidence of metastasis in TB-Tax, TB-Adr, and TB-Ava groups. Combination treatment with anti-cancer agent and NS (2.7 μg Se and 5.1 mg EPA/3.7 mg DHA/g) induced additional decreases in TB-Tax-NS, TB-Adr-NS, and TB-Ava-NS groups. Th1-associated cytokines were increased, and Th2-type cytokines were decreased significantly in TB mice with combination treatment than that of anti-cancer agent treatment alone. Combination treatment with anti-cancer agents and NS has also been shown to further increased tumor malondialdehyde (MDA) levels, lowered hypoxia-inducible factor (HIF)-1α, angiogenic markers (vascular endothelial growth factor [VEGF] and CD31) and metastatic potential, as well as reduced heat shock proteins, receptor tyrosine kinase AXL, and surface markers of cancer stem cells, and increased apoptotic proteins. For immune checkpoint molecules, combination treatment was associated with a greater decrease in programmed cell death ligand-1 (PD-L1) in both tumors and mammary glands, but PD-1 level in primary tumors was increased. Our results suggest that combination treatment with low-dose anti-cancer agents (Tax, Adr, and Ava) and oral supplementation of Se/ EPA/DHA significantly decreased tumor growth and metastatic progression in TNBC mice through multiple anti-tumor mechanisms.     

Nutritional and supranutritional levels of selenate differentially suppress prostate tumor growth in adult but not young nude mice

The inhibitory effect of oral methylseleninic acid or methylselenocysteine administration on cancer cell xenograft development in nude mice is well characterized; however, less is known about the efficacy of selenate and age on selenium chemoprevention. In this study, we tested whether selenate and duration on diets would regulate prostate cancer xenograft in nude mice. Thirty-nine homozygous NU/J nude mice were fed a selenium-deficient, Torula yeast basal diet alone (Se-) or supplemented with 0.15 (Se) or 1.0 (Se+) mg selenium/kg (as Na(2)SeO(4)) for 6 months in Experiment 1 and for 4 weeks in Experiment 2, followed by a 47-day PC-3 prostate cancer cell xenograft on the designated diet. In Experiment 1, the Se- diet enhanced the initial tumor development on days 11-17, whereas the Se+ diet suppressed tumor growth on days 35-47 in adult nude mice. Tumors grown in Se- mice were loosely packed and showed increased necrosis and inflammation as compared to those in Se and Se+ mice. In Experiment 2, dietary selenium did not affect tumor development or histopathology throughout the time course. In both experiments, postmortem plasma selenium concentrations in Se and Se+ mice were comparable and were twofold greater than those in Se- mice. Taken together, dietary selenate at nutritional and supranutritional levels differentially inhibit tumor development in adult, but not young, nude mice engrafted with PC-3 prostate cancer cells.     

Amounts of tissue magnesium and some trace elements in cats with mammary tumors related to various clinicopathological parameters

BackgroundMammary tumors are one of the major malignancies seen in cats. Researchers have indicated the similarity between the epidemiological and clinicopathological patterns of feline mammary tumors and human breast cancer (HBC). In recent years, the investigation of trace elements in cancer tissues becomes prevalent in HBC due to the role of these elements in biochemical and physiological processes. This study, it is aimed to evaluate some trace elements in feline mammary tumors according to clinical and pathological findings.MethodsA total of 60 tumoral masses from 16 female cats with mammary tumors were included in the study. The study groups were formed according to histopathology as malignant epithelial tumor (MET; n = 39) and hyperplasia and dysplasia (H&D; n = 21). Copper (Cu), Iron (Fe), Magnesium (Mg), Manganese (Mn), Selenium (Se) and Zinc (Zn) trace elements in mammary tissues were analyzed by using an inductively coupled plasma-optical emission spectrophotometer.ResultsThe mean age and weight of the cats were 11.75 ± 0.75 years and 3.35 ± 0.21 kg; respectively. Eleven of 16 cats were intact whereas the rest of them had been spayed. Metastases were observed in 10 cats. Tissue Mg level in group MET was significantly higher than in group H&D (P < 0.01) while the other elements had not significant differences between the groups. In group MET, analyzed elements were not statistically significant related to the inflammation, ulceration and invasion to the peripheral muscle (P > 0.05). However, tissue Fe level was significantly higher in T2 than in T3 (P < 0.05). The mean levels of tissue Fe, Mg and Mn had significant differences related to histological grading as P < 0.01, P < 0.05 and P < 0.001; respectively. A mild to severe correlation was found between tissue Zn and Se, Cu, Fe, Mg, and Mn levels.ConclusionTissue Mg and some trace elements were evaluated in feline mammary tumours in regard to various clinicopathological parameters. Tissue Mg level was sufficient to differentiate the malignant epithelial tumors from hyperplasia and dysplasia. However, Mn and Se tended to distinguish different tumor types. Tissue Fe, Mg and Mn had significant differences related to histological grading. Also, the Fe level was significantly higher in T2 than in T3 and Zn level tended to be higher in T3 than in T1. It was concluded that Mg, Se, Mn, Fe, Cu and Zn provided useful information on the pathogenesis of feline mammary tumors. Further research is needed on the tissue and serum concentrations of trace elements which may provide valuable information for the disease prognosis.     

Concentration levels of major and trace elements in rice from sri lanka as determined by the k 0 standardization method

Instrumental neutron activation (INAA) with k ₀ standardization has been used to determine the concentration levels of a variety of major and trace elements (Al, As, Br, Cd, Cl, Co, Cr, Cs, Cu, Fe, Hg, K, La, Mg, Mn, Mo, Na, Rb, Sc, Se, and Zn) in rice grains (raw and parboiled) and in rice flour collected from local markets in Sri Lanka. In addition, the energy-dispersive X-ray fluorescence (EDXRF) analysis has been used to determine the three elements Ca, P, and S in powdered samples. To evaluate and assure the accuracy and precision of the k ₀ standardization method, the IAEA standard reference material V-8 rye flour was analyzed. The results obtained in the present investigation were compared with the results reported from other countries. All of the elements detected in the rice matrices from Sri Lanka were very low in concentration or within normal limits for food plants. Approximate daily dietary intakes of the individual elements supplied through rice were calculated and compared with the available literature values of daily allowances.     

Effects of Mineral Supplementation on Liver Cirrhotic/Cancer Male Patients

The aim of the present study was to compare the levels of essential trace and toxic elements in biological samples (blood and serum) of male liver cirrhotic/cancer patients (n?=?144), of age groups 30?C50?years, before and after 60?days treatment with mineral supplementation. For comparison purposes, the same biological samples were also collected from healthy male subjects (n?=?120) of the same age groups. The biological samples were oxidized by 65?% HNO₃/30?% H₂O₂ (2:1) in a microwave oven. The digests of all biological samples were analyzed for arsenic (As), cadmium (Cd), selenium (Se), and zinc (Zn) by electrothermal atomic absorption spectrometry. The levels of Se and Zn were lower in liver cirrhotic/cancer patients as compared to healthy individuals (p?<?0.001). The patients with liver cirrhosis/cancer have twofold higher As and Cd levels in biological samples as compared to age-matched referents. Moreover, a negative correlation was observed between essential and toxic elements. The pathogenesis of liver cirrhosis/cancer has been associated with changes in the balance of certain essential trace and toxic elements. The study confirms that oral supplements of Se and Zn produce metabolic effects in patients with liver cirrhosis/cancer. It was observed that the status of essential trace elements, Se and Zn, was improved in biological samples of all patients after 60?days of treatment with mineral supplementation.     

Effect of Dietary Selenium and Cancer Cell Xenograft on Peripheral T and B Lymphocytes in Adult Nude Mice

Selenium (Se) is known to regulate tumorigenesis and immunity at the nutritional and supranutritional levels. Because the immune system provides critical defenses against cancer and the athymic, immune-deficient NU/J nude mice are known to gradually develop CD8⁺ and CD4⁺ T cells, we investigated whether B and T cell maturation could be modulated by dietary Se and by tumorigenesis in nude mice. Fifteen homozygous nude mice were fed a Se-deficient, Torula yeast basal diet alone (Se−) or supplemented with 0.15 (Se+) or 1.0 (Se++) mg Se/kg (as Na₂SeO₄) for 6 months, followed by a 7-week time course of PC-3 prostate cancer cell xenograft (2 × 10⁶ cells/site, 2 sites/mouse). Here, we show that peripheral B cell levels decreased in nude mice fed the Se −  or Se++ diet and the CD4⁺ T cell levels increased in mice fed the Se++ diet. During the PC-3 cell tumorigenesis, dietary Se status did not affect peripheral CD4⁺ or CD8⁺ T cells in nude mice whereas mice fed with the Se++ diet appeared to exhibit greater peripheral CD25⁺CD4⁺ T cells on day 9. Dietary Se status did not affect spleen weight in nude mice 7 weeks after the xenograft. Spleen weight was associated with frequency of peripheral CD4⁺, but not CD8⁺ T cells. Taken together, dietary Se at the nutritional and supranutritional levels regulates peripheral B and T cells in adult nude mice before and after xenograft with PC-3 prostate cancer cells.     

Obesity-Mediated Regulation of HGF/c-Met Is Associated with Reduced Basal-Like Breast Cancer Latency in Parous Mice

It is widely thought that pregnancy reduces breast cancer risk, but this lacks consideration of breast cancer subtypes. While a full term pregnancy reduces risk for estrogen receptor positive (ER+) and luminal breast cancers, parity is associated with increased risk of basal-like breast cancer (BBC) subtype. Basal-like subtypes represent less than 10% of breast cancers and are highly aggressive, affecting primarily young, African American women. Our previous work demonstrated that high fat diet-induced obesity in nulliparous mice significantly blunted latency in C3(1)-T_Ag mice, a model of BBC, potentially through the hepatocyte growth factor (HGF)/c-Met oncogenic pathway. Experimental studies have examined parity and obesity individually, but to date, the joint effects of parity and obesity have not been studied. We investigated the role of obesity in parous mice on BBC. Parity alone dramatically blunted tumor latency compared to nulliparous controls with no effects on tumor number or growth, while obesity had only a minor role in further reducing latency. Obesity-associated metabolic mediators and hormones such as insulin, estrogen, and progesterone were not significantly regulated by obesity. Plasma IL-6 was also significantly elevated by obesity in parous mice. We have previously reported a potential role for stromal-derived hepatocyte growth factor (HGF) via its cognate receptor c-Met in the etiology of obesity-induced BBC tumor onset and in both human and murine primary coculture models of BBC-aggressiveness. Obesity-associated c-Met concentrations were 2.5-fold greater in normal mammary glands of parous mice. Taken together, our studies demonstrate that, parity in C3(1)-T_Ag mice dramatically reduced BBC latency compared to nulliparous mice. In parous mice, c-Met is regulated by obesity in unaffected mammary gland and is associated with tumor onset. C3(1)-T_Ag mice recapitulate epidemiologic findings such that parity drives increased BBC risk and potential microenvironmental alterations in c-Met signaling may play a role in etiology.     

Effects of Different Selenium Application Methods on Wheat (<i>Triticum aestivum</i> L.) Biofortification and Nutritional Quality

Mineral nutrient malnutrition, especially deficiency in selenium (Se), affects the health of approximately 1 billion people worldwide. Wheat, a staple food crop, plays an important role in producing Se-enriched foodstuffs to increase the Se intake of humans. This study aimed to evaluate the effects of different Se application methods on grain yield and nutritional quality, grain Se absorption and accumulation, as well as 14 other trace elements concentrations in wheat grains. A sand culture experiment was conducted via a completely randomized 3 × 2 × 1 factorial scheme (three Se levels × two methods of Se application, foliar or soil × one Se sources, selenite), with two wheat cultivars (Guizi No.1, Chinese Spring). The results showed that both foliar Se and soil Se application methods had effects on wheat pollination. Foliar Se application resulted in early flowering of wheat, while soil Se application caused early flowering of wheat at low Se levels (5 mg kg⁻¹ ) and delayed wheat flowering at high selenium levels (10 mg kg⁻¹ ), respectively. For trace elements, human essential trace elements (Fe, Zn, Mn, Cu, Cr, Mo, Co and Ni) concentrations in wheat grains were dependent of Se application methods and wheat cultivars. However, toxic trace elements (Cd, Pb, Hg, As, Li and Al) concentrations can be decreased by both methods, indicating a possible antagonistic effect. Moreover, both methods increased Se concentrations, and improved grain yield and nutritional quality, while the foliar application was better than soil. Accordingly, this study provided useful information concerning nutritional biofortification of wheat, indicating that it is feasible to apply Se to conduct Se biofortification, inhibit the heavy metal elements concentrations and improve yield and quality in crops, which caused human health benefits.