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Review of vitamin E and selenium in the prevention of prostate cancer: implications of the selenium and vitamin E chemoprevention trial.

The National Cancer Institute in cooperation with the Southwest Oncology Group has begun one of the largest prostate cancer prevention studies to date, the Selenium and Vitamin E Chemoprevention Trial (SELECT). The purpose of this article is to review the evidence and discuss the individual antioxidant compounds under study. The authors comprehensively reviewed the peer-reviewed literature on the chemoprevention of prostate cancer with emphasis on the antioxidants vitamin E and selenium. The credible leads for the primary prevention of prostate cancer using selenium and vitamin E have emerged as secondary findings from randomized controlled trials with corroborative evidence from observational and in vitro studies. Selenium and vitamin E are widely available compounds that are safe if taken in moderation, with relatively few adverse effects. The evidence in support of the antioxidants in the primary prevention of prostate cancer is promising, and the next step in definitively answering the question has been addressed by the investigators of SELECT. The SELECT study will define the role of the antioxidants selenium and vitamin E in the prevention of prostate cancer; complete data from the study will be available in 12 years.

Antioxidants↗

Selenium levels in blood of upper Silesian population: evidence of suboptimal selenium status in a significant percentage of the population.

The selenium status and the relationship of whole-blood selenium and plasma homocysteine are reported for healthy human subjects living in Upper Silesia. A total of 1063 individuals (627 male and 436 female) examined for whole-blood selenium were subdivided into six groups according to age; the youngest included adolescents (n=143) aged 10-15 yr, and the oldest were centenarians (n=132). The mean Se content was relatively low (62.5+/-18.4 microg/L), and it tended to be higher in men (65.9+/-17.2 microg/L) than in women (57.5+/-18.9 microg/L). Selenium levels appeared to be age dependent, as the highest values were observed in young and middle-age adults (21-40 yr), whereas they were significantly lower in adolescents and in the elderly. In more than 40% of apparently healthy adults (aged 21-69 yr), the Se concentration was within the range 60-80 microg/L (i.e., below the lower limit of the nutritional adequacy range [80 microg/L]). A significant inverse correlation between whole-blood selenium and plasma total homocysteine was detected in a smaller population sample of middle-aged and elderly persons (n=204).

Adolescent↗

Effect of intraruminally administered, selenium soluble-glass boluses on selenium status in cows and their calves.

Intraruminal selenium soluble-glass boluses were administered by balling gun to 65 of 125 crossbred beef cows (Shorthorn X Charolais) during the last trimester of pregnancy. Elevated (P less than .01) whole blood glutathione peroxidase (GSH-Px) concentrations were observed monthly for the next 10 mo following initiation of treatment, reaching the maximum magnitude (263 vs 41) at the fourth month. Monthly milk samples showed elevated selenium concentrations (P less than .01, April through August; P less than .05 through September). Intraruminal, selenium soluble-glass bolus administration to gestating cows was highly effective in raising the selenium status of their progeny. Although the control calves were in low-selenium status, no acute cases of nutritional muscular dystrophy were observed during this experiment.

Administration, Oral↗

Selenium intake and urinary excretion in persons living near a high selenium area.

Selenium intake by adults consuming self-selected levels of four different diets averaged 209 micrograms. per day and correlated well with caloric and protein intake. Urinary selenium concentration averaged 0.108 microgram. per milliliter, and 24-hour excretion for the various diets averaged 58.0% to 88.6% of the intake. The data suggest that the RDA upper limit of 200 micrograms. of selenium per day and the suggested maximum urine selenium concentration may be too restrictive. The data further indicate that even though there are differences in the absorption of selenium from different sources, the average is about 70% for foods purchased in the Northern Great Plains area.

Adult↗

[Studies on the correlation of blood selenium and lung cancer. II. An analysis of serum selenium levels and influencing factors in patients with lung cancer].

This paper reports the serum selenium concentration in 100 cases of lung cancer patients and 100 healthy controls. The results showed that the serum selenium level in patients with lung cancer was significantly lower than that of controls. Serum selenium level in lung cancer patients was inversely related to the stage of cancer, the amount of tobacco abuse and the serum Cu level. It was positively correlated with patient's nutritional status and the serum albumin level. Serum selenium level was decreased with cancer progression and increased with disease remission. These results suggest that the lower serum selenium level in lung cancer patients was the result rather than the cause of cancer.

Adenocarcinoma↗

[Levels of selenium in urine after treatment of pityriasis versicolor with a 1.0% selenium sulfide].

The treatment of pityriasis versicolor by the topical application of selenium sulfide 1% was studied in two groups of patients. Diagnosis and response to therapy was determined by clinical observation. Wood's light fluorescence, and direct microscopic examination. The efficacy of three different therapeutic regimes was studied in one group by the application of the drug to the entire skin for either five minutes, fifteen minutes, or twelve hours for eighteen days. Each method proved equally effective in resolving the infection. Therefore, the cutaneous application of selenium sulfide 1 % for five minutes daily for eighteen days is the recommended treatment for pityriasis versicolor. The percutaneous absorption of selenium sulfide was also studied in another groups who applied the drug to the entire skin for five minutes for eighteen days. Fluorimetric analysis of urinary samples collected on the third and thirteenth days of treatment revealed no significant increase in the excretion of selenium as compared to pretreatment levels. Systemic toxicity was not observed in any of the patients treated. The results suggest that the selenium sulfide is absorbed poorly from the skin and is a safe and effective therapy for pityriasis versicolor.

Adult↗

Selenium species bioaccessibility in enriched radish (Raphanus sativus): a potential dietary source of selenium.

An in vitro gastrointestinal method was employed to predict the potential bioavailability of selenium and its species from radish, belonging to the Brassicaceae family, grown in hydroponics media in the presence of inorganic selenium, such as Na2SeO3 and Na2SeO4. A low transformation of Se into organic forms was observed in radish plants grown in Se(VI)-enriched culture media. On the contrary, in those plants exposed to selenite, >95% of the total selenium was found as selenocystine (SeCys2), selenomethionine (SeMet), and Se-methylselenocysteine (SeMetSeCys). The concentrations of these species in fresh samples remained almost unaltered after a simulated gastrointestinal digestion. Therefore, a high selenium content of Se-methylselenocysteine (65%), previously reported as a cancer chemopreventive species, remained in the potentially bioabsorbable fraction. As these plants usually undergo a short development cycle, these results suggest that radish enriched in selenite could be a good choice as an organoselenium supplement for the human diet and animal feed.

Biological Availability↗

Preliminary study on the determination of selenium compounds in some selenium-accumulating mushrooms.

Using various chromatographic techniques (size exclusion, anion exchange, and cation exchange) combined with several detectors (neutron activation analysis and atomic fluorescence spectrometry), an attempt was made to characterize selenium compounds in some edible, selenium-accumulating mushrooms (Albatrellus pes-caprae and Boletus edulis). The mushrooms contained mostly low-molecular-weight (6 kDa) selenium compounds. After proteolysis, only a small fraction of the extractable selenium could be identified as selenite (3.0-9.2%, Albatrellus pes-caprae), selenocystine (minor, Albatrellus pes-caprae; 7.5%, Boletus edulis), or selenomethionine (1.0%, Boletus edulis), leaving the form of the bulk still to be elucidated.

Agaricales↗

Selenium is involved in the negative regulation of the expression of selenium-free [NiFe] hydrogenases in Methanococcus voltae.

Competitive polymerase chain reactions (PCR) were used to analyze quantitatively the transcription patterns of the four different gene groups encoding [NiFe] hydrogenases in Methanococcus voltae. In cells growing in the presence of selenium, transcripts of only two of the hydrogenase transcription units could be detected in quantities above background levels. The missing transcripts encode the selenium-free F420-non-reducing and F420-reducing hydrogenases. In cells grown without selenium these transcripts are detectable, indicating the involvement of selenium in their transcriptional regulation.

Base Sequence↗

[Selenium concentration in erythrocytes of patients with rheumatoid arthritis. Clinical and laboratory chemistry infection markers during administration of selenium].

PATIENTS AND METHODS: Seventy patients with definitive rheumatoid arthritis were matched to built 2 groups, which were double-blind and randomized allocated to supplementation with sodium-selenit 200 micrograms/d or placebo for 3 months, each. Both groups were given fish oil fatty acids (30 mg/kg body weight), DMARDS were continued throughout the study, while variations in steroids or NSAD were admitted. RESULTS: Selenium concentrations in erythrocytes of patients with rheumatoid arthritis were 85.1 +/- 26 micrograms/l, and significantly lower than found in an average German population (123 +/- 23 micrograms/l). During the observation period of 3 months normal selenium concentrations were not restored, despite supplementation higher than RDA. At the end of the experimental period the selenium supplemented group showed less tender or swollen joints, and morning stiffness. Selen-supplemented patients needed less cortisone and NSAD than controls. In accordance with clinical improvement we found a decrease of laboratory indicators of inflammation (C-reactive protein, alpha 2-globuline, prostaglandin E2). CONCLUSION: No side effects of supplementation with selenium were noted, which can be considered as adjuvant therapy in patients with rheumatoid arthritis.

Adult↗

Electrochemical vapor generation of selenium species after online photolysis and reduction by UV-irradiation under nano TiO2 photocatalysis and its application to selenium speciation by HPLC coupled with atomic fluorescence spectrometry.

An online UV photolysis and UV/TiO2 photocatalysis reduction device (UV-UV/TiO2 PCRD) and an electrochemical vapor generation (ECVG) cell have been used for the first time as an interface between high-performance liquid chromatography (HPLC) and atomic fluorescence spectrometry (AFS) for selenium speciation. The newly designed ECVG cell of approximately 115 microL dead volume consists of a carbon fiber cathode and a platinum loop anode; the atomic hydrogen generated on the cathode was used to reduce selenium to vapor species for AFS determination. The noise was greatly reduced compared with that obtained by use of the UV-UV/TiO2 PCRD-KBH4-acid interface. The detection limits obtained for seleno-DL: -cystine (SeCys), selenite (Se(IV)), seleno-DL: -methionine (SeMet), and selenate (Se(VI)) were 2.1, 2.9, 4.3, and 3.5 ng mL(-1), respectively. The proposed method was successfully applied to the speciation of selenium in water-soluble extracts of garlic shoots cultured with different selenium species. The results obtained suggested that UV-UV/TiO2 PCRD-ECVG should be an effective interface between HPLC and AFS for the speciation of elements amenable to vapor generation, and is superior to methods involving KBH4.

Catalysis↗

Comparing a selenium accumulator plant (Brassica juncea) to a nonaccumulator plant (Helianthus annuus) to investigate selenium-containing proteins.

Selenoproteins have been identified in a diverse range of organisms, including bacteria and animals. Their occurrence and role in the plant kingdom are, however, less well-understood. This work investigated the water-soluble selenium-containing proteins extracted from a selenium-accumulating plant species (Brassica juncea) and a nonaccumulator species (Helianthus annuus) exposed to varying forms and concentrations of selenium. Firstly, protein extracts were analyzed by size exclusion chromatography coupled to inductively coupled plasma mass spectrometry; specific detection was achieved by monitoring characteristic isotopes. Then, proteolytic digests of the plant extracts were analyzed by reversed phase chromatography coupled to ICP-MS in order to investigate selenoamino acid and selenopeptide content. Selenomethionine was observed to be the primary constituent of the proteins of the nonaccumulator plant, while selenocystine and selenomethionine were found in the same proportion in the accumulator extract. One main selenium-containing species was present at higher levels in the root digests than in the leaf digests; levels were greater in the nonaccumulator than in the accumulator plant.

Chromatography, High Pressure Liquid↗

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.

Animals↗

Determination of selenium in blood serum of children with acute leukemia and effect of chemotherapy on serum selenium level.

The concentration of selenium in serum was measured by the neutron activation method in three groups of children: 30 healthy children, 20 children with Acute Myeloblastic Leukemia (AML) and 40 with Acute Lymphoblastic Leukemia (ALL) (L1; n = 20, L2; n = 20). The samples were taken before and after induction chemotherapy. Age, sex, FAB, initial WBC, BUN, creatinine and urinary analysis did not show a significant change in the amount of selenium in serum. Selenium concentration in serum samples of ALL children before chemotherapy showed no significant differences as compared with that of normal individuals, but there were significant differences between children with AML and normal individuals (76.46 +/- 24.59 micrograms/L vs 102.38 +/- 19.25 micrograms/L, with p < 0.02). In conclusion, the question of whether these deficiencies are responsible for the disease or are the result of a secondary effect of the cancer remain to be answered. Immediately after induction chemotherapy, the selenium concentration in the serum of ALL children decreased significantly (80.14 +/- 15.48 micrograms/L vs 110.72 +/- 28.3 micrograms/L, p < 0.001), but this was not the case for AML children. These findings may be due to the difference in the drugs administered in induction chemotherapy of ALL and AML children.

Antineoplastic Agents↗

Areas with high concentrations of selenium in the soil and forage produce beef with enhanced concentrations of selenium.

Beef provides a significant portion of human dietary selenium (Se), and it is possible that modest portions of beef produced in areas with high-Se soil and forage could provide the entire Recommended Dietary Allowance (RDA) for Se. The present study has addressed the environmental conditions that resulted in the production of high-Se beef. One hundred and thirty-eight cull cows were obtained from 21 ranches in five distinct geographic regions that, on the basis of soil parent material, reports of Se deficiency, and previous soil and forage Se surveys, were likely to have high or low Se concentrations in the soil. Grass and soil samples were taken from ranch sites, and hair, whole blood, skeletal muscle, diaphragm muscle, and liver samples were obtained from the animals. Hair and whole blood samples were taken 1 day prior to shipping. Selenium concentrations of all samples were determined by hydride generation atomic absorption spectroscopy. Geographic origin affected Se content of all samples (p < 0.05). Selenium concentrations in soil (r = 0.53; p < 0.01) and grass (r = 0.63; p < 0.01) were correlated to Se content of skeletal muscle. Selenium concentrations in whole blood, diaphragm, hair, and liver also were significantly correlated to Se content of skeletal muscle (p < 0.01). Cows that received Se in mineral supplements did not have significantly higher concentrations of Se in sampled tissues (p > 0.05). Results of this study suggest that the greatest source of variation in Se content of bovine skeletal muscle was the geographic region from which the beef originated and not production or management practices. Results also demonstrated that a 100 g serving of high-Se beef could provide 100% of the RDA for Se.

Animal Feed↗

Intramolecular homolytic substitution at selenium: synthesis of novel selenium-containing vitamin E analogues.

Treatment of 1-(benzylselenenyl)-5-butyl-5-nonanol (10) with oxalyl chloride followed by the sodium salt of N-hydroxypyridine-2-thione afforded the corresponding pyridine-2-thione-N-oxycarbonyl (PTOC) oxalate ester which was not isolated but immediately heated to provide 2,2-dibutylselenane (7). This transformation presumably involves a tertiary alkyl radical that undergoes intramolecular homolytic substitution at selenium with loss of the benzyl radical to provide the selenium-containing ring system (7). A similar protocol, when applied to 1-(2-benzylselenenyl-5-methoxyphenyl)-3-methyl-3-heptanol (18) and 1-(2-benzylselenenyl-5-methoxyphenyl)-3,7,11,15-tetramethyl-3-hexadecanol (19), followed by deprotection, afforded the selenium-containing alpha-tocopherol analogues 4 and 1f, respectively, in moderate yields. To the best of our knowledge, these transformations represent the first examples of tertiary radicals involved in homolytic substitution chemistry at selenium.

Heterocyclic Compounds↗

Correlations between parameters of body selenium status and peripheral thyroid parameters in the low selenium region.

The following were measured in 380 male and female inhabitants of Prague (n the age range 6-65 years):selenium in serum and urine, iodine in urine, thyroid-stimulating hormone, thyroid volume, thyroxine (T4), triiodothyronine (T3), ankle jerk time, pulse rate and body fat. Correlations were calculated to assess the influence of Se upon the thyroid hormone parameters and their peripheral effects in Se-deficient regions both by using the linear correlation analysis and by using the multiple linear correlation analysis and the analysis of variance. Many significant linear correlations were found for whole groups of examined persons, for the individual groups (boys, men, girls and women) as well as for subgroups, according to the age and sex. We conclude, from the analytical results of Se indices (serum, hair, urine) reported previously, and on the basis of the statistical demonstration of the influence of selenium upon thyroid hormone levels and the peripheral effects in the group of Prague inhabitants in connection with the previously documented role of Se in pathways resulting in the synthesis of physiologically active thyroid hormone, that inhabitants of Prague are selenium deficient. Concurrent deficiency of selenium may modify and even worsen iodine deficiency disorders of various stages. Multiple linear correlation analysis followed by analysis of variance of subgroups indicated a coincidence of the effects of some measured parameters upon the peripheral manifestation of thyroid hormone state as well as highlighting the effect of other independent variables of thyroid hormone metabolism than those measured in the study.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

DNA sequencing of a mouse liver protein that binds selenium: implications for selenium's mechanism of action in cancer prevention.

Complementary DNA clones for liver protein 56K (SLP-56) were isolated by screening a lambda Zap mouse liver library. The cloned cDNAs represented the complete message. The correct reading frame was verified by alignment of the deduced amino acid sequence with that of peptides sequenced from the purified protein. The primary sequence has not been reported previously since homologous DNA sequences were not found in GenBank. Most importantly, the DNA sequence did not contain an in-frame TGA codon that would code for seleno-cysteine, as occurs in the prototypic selenoprotein, glutathione peroxidase. Hydropathy analysis suggested the protein was not a membrane-spanning protein. SLP-56 was previously localized as a cytosolic-soluble protein on the basis of cell fractionation experiments. The results suggest that SLP-56 is different from proteins whose synthesis and concentration are dependent upon selenium and require TGA to encode for selenocysteine. In this respect, SLP-56 appears to be similar to liver fatty acid binding protein (SLP-14) for which selenium is a ligand. Our working hypothesis is that selenium exerts its inhibitory effects on cell growth by modulating the properties of existing growth regulatory proteins. The two proteins that are readily labeled by selenium in many rodent tissues, SLP-56 and SLP-14, would fit into this category.

Amino Acid Sequence↗