Cancer-protective properties of high-selenium broccoli.

Selenium (Se) from high-Se garlic reduces the incidence of chemically induced mammary tumors, and Se from high-Se broccoli reduces colon cancer. However, the ability of Se from high-Se broccoli to protect against mammary cancer has not been tested. Also, the sprout form of broccoli contains many secondary plant compounds that are known to reduce cancer risk, but the anticarcinogenic activity of broccoli sprouts has not been investigated. The present studies examined the ability of high-Se broccoli or high-Se broccoli sprouts to protect against chemically induced mammary or colon cancer. In one experiment, Sprague--Dawley rats that consumed diets containing 3.0 microg of Se/g supplied as high-Se broccoli had significantly fewer mammary tumors than rats fed 0.1 microg of Se as selenite with or without the addition of regular broccoli. In the second experiment, Fisher F-344 rats fed 2.0 microg of Se/g of diet supplied as either high-Se broccoli florets or high-Se broccoli sprouts had significantly fewer aberrant colon crypts than rats fed 0.1 or 2 microg of Se/g of diet supplied as selenite with or without the addition of low-Se broccoli. These data demonstrate that the cancer-protective effect of Se in high-Se broccoli extends to mammary cancer and the protective forms of broccoli against colon cancer include high-Se broccoli sprouts.

Chemical speciation influences comparative activity of selenium-enriched garlic and yeast in mammary cancer prevention.

A recent human intervention trial showed that daily supplementation with selenized yeast (Se-yeast) led to a decrease in the overall cancer morbidity and mortality by nearly 50%; past research has also demonstrated that selenized garlic (Se-garlic) is very effective in mammary cancer chemoprevention in the rat model. The goal of this study was to compare certain biological activities of Se-garlic and Se-yeast and to elucidate the differences based on the chemical forms of selenium found in these two natural products. Characterization of organic selenium compounds in yeast (1922 microg/g Se) and garlic (296 microg/g Se) was carried out by high-performance liquid chromatography with inductively coupled plasma mass spectrometry or with electrospray mass spectrometry. Analytical speciation studies showed that the bulk of the selenium in Se-garlic and Se-yeast is in the form of gamma-glutamyl-Se-methylselenocysteine (73%) and selenomethionine (85%), respectively. The above methodology has the sensitivity and capability to account for >90% of total selenium. In the rat feeding studies, supplementation of Se-garlic in the diet at different levels consistently caused a lower total tissue selenium accumulation when compared to Se-yeast. On the other hand, Se-garlic was significantly more effective in suppressing the development of premalignant lesions and the formation of adenocarcinomas in the mammary gland of carcinogen-treated rats. Given the present finding on the identity of selenomethionine and gamma-glutamyl-Se-methylselenocysteine as the major form of selenium in Se-yeast and Se-garlic, respectively, the metabolism of these two compounds is discussed in an attempt to elucidate how their disposition in tissues might account for the differences in cancer chemopreventive activity.

Toxic and nutrient element concentrations in soft tissues of zebra and quagga mussels from Lakes Erie and Ontario.

Zebra and quagga mussels were collected from Lakes Erie and Ontario in 1997 and the soft mussel tissues were analyzed for Ca, Cd, Cr, Cu, Fe, Hg, K, Mg, Mn, Mo, Na, Ni, Pb, Se, Sr, V and Zn. No consistent relationships were apparent when comparing element concentrations in soft mussel tissues and mussel type, size range or sampling location. Literature dealing with the absorption of metals by both mussel types is reviewed.

Chemoprevention with triphenylselenonium chloride in selenium-deficient rats.

Cancer chemoprevention by high levels of selenium, including compounds like sodium selenite or selenomethionine, is generally not accompanied by increases in known selenoenzymes. There has been no information on whether selenoenzymes are obligatory mediators of the anticarcinogenic effect of selenium. Our previous experience with triphenylselenonium chloride suggests that it might be an ideal agent for studying selenium chemoprevention while simultaneously precluding the synthesis of selenoenzymes. Triphenylselenonium chloride has excellent tumor inhibitory activity but does not support the repletion of selenoenzymes in animals that have been deprived of a bioavailable form of selenium. In the present experiments, we evaluated the efficacy of mammary cancer protection by this compound in rats fed either a selenite-deficient (< 0.01 ppm Se) or selenite-adequate (0.1 ppm Se) diet. We also measured the activities of liver glutathione peroxidase and thioredoxin reductase as markers of selenium bioavailability in these different treatment conditions. In carcinogen-treated control animals not receiving triphenylselenonium chloride, mammary tumor incidence and the total number of tumors were similar between the selenite-deficient and selenite-adequate groups. Thus the correction of selenium deficiency by the addition of 0.1 ppm Se as selenite did not have detectable anticarcinogenic effects. Supplementation of triphenylselenonium chloride at a level of 30 ppm Se suppressed mammary tumorigenesis by approximately 50% regardless of dietary selenium nutritional status. However, this supplement had little effect on tissue selenium levels and did not increase liver glutathione peroxidase or thioredoxin reductase activities. In contrast, a level of 0.1 ppm Se as selenite did not affect mammary tumorigenesis but markedly increased tissue selenium concentrations and selenoenzyme activities. It is concluded that triphenylselenonium chloride does not release inorganic selenium for selenoprotein synthesis and that its anticancer activity involves mechanisms that are probably intrinsic to the compound. This study also shows for the first time that selenium chemoprevention is possible in an environment of severely depressed selenoenzyme expression. Thus selenium chemoprevention efficacy can be separated experimentally from selenoprotein synthesis using this model system.

Urinary mutagenicity as an indicator of occupational exposure in a cohort of cosmetologists.

Epidemiological studies suggest a higher risk of hematopoietic disorders including lymphoma among cosmetologists. The etiology of these disorders among cosmetologists is unknown, but beauticians are exposed to a wide variety of chemicals in the workplace. In this study, the urinary mutagenicity of cosmetologists was studied as an indicator of occupational exposure. A microsuspension modification of the Ames assay with Salmonella typhimurium strain TA98 was used to detect direct-acting mutagens and promutagens in urine. A comparable group of teachers of similar age and gender, and living in the same geographic area was used as the control group. There was no elevated risk for urinary mutagenicity among the cosmetologists after controlling for a number of confounders including smoking. In a multivariate model, smoking regularly or within 24 h of sample collection was found to be positively associated with urinary mutagenicity among both groups. The number of cigarettes smoked daily, age, and length of employment were not associated with urinary mutagenicity. Analysis of urine samples collected successively from each participant showed a fair to good agreement between promutagens in samples, suggesting a fairly constant exposure to promutagens.

Mercury content of smelt in Cayuga Lake in central New York State.

Smelt (Osmerus mordax) were netted from Cayuga Lake in Central New York State and analyzed for mercury concentration. There was no statistical significance (p > 0.05) when attempting to correlate mercury concentration with fish length or weight for either sex. Factors affecting methylation, demethylation and absorption of mercury are discussed.

Activities of structurally-related lipophilic selenium compounds as cancer chemopreventive agents.

The present study compared the effects of four lipophilic forms of selenium with regard to cancer chemopreventive activity, tissue selenium accumulation, and bioavailability for synthesis of a selenoprotein. These reagents included methylphenyl selenide, diphenyl selenide, triphenyl-selenonium chloride, and p-xylylbis(methylselenide). The maximum tolerable dose (added in the diet) for each of these compounds was 5, 30, > 200, and 5 ppm Se, respectively. Because of differences in their tolerance, the cancer chemopreventive activities (in a methylnitrosourea-induced mammary tumor model in rats) of all 4 compounds were assessed at the 5 ppm Se level. Methylphenyl selenide was the most effective--79% inhibition, followed by p-xylylbis-(methylselenide)--66% inhibition, triphenylselenonium chloride--27% inhibition, and diphenyl selenide--10% inhibition. With respect to tissue selenium levels, p-xylylbis(methylselenide) produced the highest accumulation of selenium (approximately 3-fold increase in liver and kidney, 14-fold increase in mammary gland); methylphenyl selenide and diphenyl selenide showed more modest increases (1.5-fold or less in liver and kidney, 2.5-fold or less in mammary gland); while triphenylselenonium chloride resulted in no change. Highest bioavailability of selenium was observed for p-xylylbis(methylselenide), which was followed closely by methylphenyl selenide. Bioavailability was very low with diphenyl selenide, and undetectable with triphenylselenonium chloride. The chemical reactivities of these different selenium compounds are discussed in relation to the biological effects reported here.

Triphenylselenonium and diphenylselenide in cancer chemoprevention: comparative studies of anticarcinogenic efficacy, tissue selenium levels and excretion profile.

The objectives of the present study were to evaluate the cancer chemopreventive activity of triphenylselenonium chloride and diphenylselenide and to investigate the pharmacology of these two compounds with respect to their tissue accumulation and excretion profile. Although both phenyl selenide derivatives are related to each other structurally, they differ substantially in their intrinsic chemical properties. Triphenylselenonium is positively charged and amphiphilic, while diphenylselenide is uncharged and lipophilic. With the use of either the DMBA- or MNU-induced mammary tumor model in rats, triphenylselenonium was found to have superior chemopreventive efficacy compared to diphenylselenide. Both reagents were present at 30 ppm Se in the diet. At the time of sacrifice (22 weeks post-carcinogen), triphenylselenonium produced only minimal accumulation of selenium in the liver, kidney, mammary gland and plasma. In contrast, diphenylselenide caused a 2- to 3-fold elevation in selenium concentration depending on the tissue examined. Thus even though diphenylselenide was able to increase total selenium in tissues, it was less active in cancer protection. Fecal excretion following a single oral dose of triphenylselenonium (equal to the amount consumed in 1 day by an animal fed a diet containing 30 ppm Se) was approximately 78% and 8% of the dose during the first and second day, respectively, suggesting that the bulk of the dose was not absorbed. With diphenylselenide, fecal excretion was about 6% and 30% of the dose during the first and second day, and about 20% of the dose was excreted in the urine in each of the 2 days. This observation suggests that a large proportion of the diphenylselenide dose was absorbed and that urinary excretion was a major route of elimination for diphenylselenide once it was absorbed. Further studies are needed to clarify the basis for the differential effects of these phenyl selenide derivatives.

Modulation of phase I and phase II xenobiotic-metabolizing enzymes by selenium-enriched garlic in rats.

Previous research showed that treatment with selenium-enriched garlic (Se-garlic) was able to inhibit the initiation phase of mammary carcinogenesis in the dimethyl-benz[a]anthracene (DMBA) model in rats. The present study was designed to investigate the following parameters: 1) DMBA-DNA adduct formation in liver and mammary gland, 2) urinary excretion of DMBA metabolites, 3) phase I and phase II xenobiotic-metabolizing enzymes, and 4) tissue selenium levels as a function of Se-garlic supplementation. Prior feeding with an Se-garlic-containing diet (at 3 ppm Se) for two weeks resulted in a consistent reduction of all DMBA adducts in liver and mammary gland. This was accompanied by a 40% increase in urinary excretion of DMBA metabolites over a two-day period. Several liver P-450 enzymes were examined in rats fed a diet supplemented with 1, 2, or 3 ppm Se. Compared with controls receiving 0.1 ppm Se, no significant alteration in activity was detected with respect to P-450 1A1 (responsible for DMBA activation), 1A2, 2B1, 2E1, and 3A4. In contrast, glutathione S-transferase and uridine 5'-diphosphate-glucuronyltransferase activities were elevated to a maximum of 2- to 2.5-fold in liver and kidney. As expected, there was a dose-dependent elevation of selenium concentrations in liver, kidney, mammary gland, and plasma as a function of the level of Se-garlic supplementation. Our data seem to suggest that an increased detoxification of carcinogen via the phase II conjugating enzymes might represent a mechanism of tumor suppression by Se-garlic.

Effect on an aqueous extract of selenium-enriched garlic on in vitro markers and in vivo efficacy in cancer prevention.

Previous work has shown that the efficacy of cancer prevention by selenium-enriched garlic (Se-garlic) is primarily dependent on the action of selenium. An aqueous extract containing 43 micro Se/ml was prepared from lyophilized Se-garlic powder by the Soxhlet method. The activity of this Se-garlic extract was evaluated in a transformed mammary epithelial cell culture model for its effect on cell morphology, cell growth, cell cycle progression and the induction of single and double stranded breaks in DNA. Comparisons were also made with a similarly prepared extract from regular garlic, Se-methylselenocysteine (a major water-soluble seleno-amino acid identified in Se-garlic) and selenite (used for fertilizing Se-garlic). In contrast to the regular garlic extract which produced little or no modulation of the above parameters, treatment with the Se-garlic extract resulted in growth inhibition, GI phase cell cycle arrest and apoptotic DNA double strand breaks in the absence of DNA single strand breaks. This pattern of cellular responses was duplicated with exposure to Se-methylselenocysteine. Selenite, on the other hand, induced cell cycle blockage in the S/G2-M phase, and a marked increase in DNA single strand breaks (a measure of genotoxicity) in addition to growth suppression. The chemopreventive efficacy of the two garlic extracts was also investigated in the rat methylnitrosourea mammary tumor model. Both extracts were supplemented in the diet for 1 month immediately following carcinogen administration. Significant cancer protection was observed with treatment by the Se-garlic extract (at 3 p.p.m. Se in the diet), while little benefit was noted with treatment by the regular garlic extract. Based on the above in vitro and in vivo findings, it is hypothesized that the Se-garlic extract, in part via the action of Se-methylselenocysteine, is able to inhibit tumorigenesis by suppressing the proliferation and reducing the survival of the early transformed cells. Furthermore, the data also support the concept that the modulation of certain in vitro markers may be of value in predicting the effectiveness of novel forms of selenium for cancer prevention.

Selenium-enriched garlic inhibits the early stage but not the late stage of mammary carcinogenesis.

Previous work has shown that the efficacy of cancer prevention by selenium-enriched garlic (Se-garlic) is primarily dependent on the action of selenium. Additionally, supplementation of Se-garlic inhibited the post-initiation phase of mammary carcinogenesis when it was given continuously to the animals. In this report, experiments were carried out in which treatment with the Se-garlic was started after carcinogen dosing (DMBA or MNU) but was restricted to either the early or late stage of neoplastic progression. The results from these two models showed that a short-term exposure to the Se-garlic for 1 month immediately following carcinogen administration was just as effective in cancer prevention as the continuous exposure regimen (5 months), suggesting that the Se-garlic may irreversibly alter the process of clonal expansion and/or selection of transformed cells during their early stage of development. Plasma and mammary tissue selenium levels essentially returned to basal levels at 1 month after withdrawal of supplementation. These observations imply that the outcome of cancer protection by short-term Se-garlic intervention was not due to a slow turnover, and therefore a lingering presence, of selenium in the target organ or in the circulation. The above finding was in contrast to that of a second study in which Se-garlic was supplemented starting at 13 weeks after carcinogen treatment. With this protocol, the number of new tumors and the number of new tumor-bearing rats found during the intervention period (weeks 13 to 22) were not statistically different between the control and supplemented groups, suggesting that Se-garlic had a minimal effect on the later stages of mammary carcinogenesis.

Efficacy of cancer prevention by high-selenium garlic is primarily dependent on the action of selenium.

We reported previously that garlic cultivated with selenite fertilization showed powerful chemopreventive activity in the rat dimethylbenz[a]anthracene (DMBA)-induced mammary tumor model (Carcinogenesis 15, 573-576, 1994). In order to ascertain that the efficacy of the high-selenium garlic in cancer protection is primarily dependent on the action of selenium we compared the effects of two batches of garlic powder with marked differences in their level of selenium enrichment, 112 or 1355 p.p.m. Se dry weight. Both products were added to the diet to achieve the same final concentration of 2 p.p.m. Se. The supplementation protocol was designed to evaluate the efficacy during either the initiation phase or post-initiation phase of DMBA mammary carcinogenesis. Significant tumor reduction was observed with either treatment protocol. Furthermore, the magnitude tumor suppression, as well as the extent of DMBA-DNA adduct inhibition, were very similar with the two batches of garlic, even though the amounts of garlic in the diet varied considerably between them (1.8% for the 112 p.p.m. Se garlic versus 0.15% for the 1355 p.p.m. Se garlic). This suggests that the anti-cancer activity of the high-selenium garlic was likely to be accounted for by the effect of selenium, rather than the effect of garlic per se. A continuous feeding of the high-selenium garlic produced a modest increase in total selenium in various tissues. In general the profile of selenium accumulation was comparable in rats ingesting either the 112 or the 1355 p.p.m. Se garlic. Thus, based on the results of several biological responses, it appears that the ability of the high-selenium garlic to protect against tumorigenesis is primarily dependent on increased intake of selenium provided by the vegetable. Future research will be focused on the chemical form of selenium in the garlic.

Selenium content of Brazil nuts from two geographic locations in Brazil.

Brazil nuts (Bertholletia excelsa) natively contain very high concentrations of selenium. Since dietary selenium, including Brazil nuts, have been associated with protection against tumor development in laboratory animal studies, it was of interest to determine the selenium content of the nuts from different nut-growing regions of Brazil. In the work reported, 162 nuts from each of two regions (Acre-Rondonia and Manaus-Belem) were individually analyzed for selenium. The average +/- standard deviation and range of selenium concentrations in ppm, fresh weight for nuts from Acre-Rondonia and Manaus-Belem regions were, respectively, 3.06 +/- 4.01 (0.03-31.7) and 36.0 +/- 50.0 (1.25-512.0). The toxicology of Brazil nut consumption is discussed.

Residues of arsenic and lead in potato soils on Long Island.

Sodium arsenite was used for vine control and fall weed control in potatoes on Long Island for many years. Lead arsenate may also have been used as an insecticide in certain areas. A study was conducted to determine remaining concentrations of arsenic and lead in potato soils on Long Island. The total concentrations of both arsenic and lead were markedly higher in the soils sampled than in untreated control soils. The behavior of arsenic and lead in soils is discussed.

Analytical survey of elements in veterinary college incinerator ashes.

While appreciable attention has been given to the elemental composition of ashes from municipal solid waste incinerators, relatively little information is available on the elemental content of incinerators burning animal carcasses and medical wastes. In the work reported here, an analytical survey was conducted of the concentration of 22 elements in the ashes of incinerators located at veterinary colleges or animal disease diagnostic laboratories in seven states. With the exception of Zn, the concentrations of most elements were well below those found in ashes from municipal solid waste incinerators. Conversely, Ca, P and K were much higher in concentration probably deriving largely from bones, teeth and other organs of animals. There was an indication that burned plastic wastes were a source of Pb in the ashes. The concentrations of several toxic elements varied widely probably due to variations in initial waste composition, incinerator design and operating parameters. The concentrations of soluble salts in the ashes were appreciable. Organic matter in the ashes was low to nondetectable indicating the completeness of incineration.

Enrichment of selenium in allium vegetables for cancer prevention.

We previously reported that garlic cultivated with selenium fertilization is superior to regular garlic in mammary cancer prevention in the rat 7,12-dimethylbenz[a]anthracene (DMBA) model (Nutr. Cancer, 17, 279-286, 1992). A new crop of high-selenium garlic was harvested in 1992 and was used in a dose-response study to confirm the reproducibility of the product and the bioassay. Supplementation of 1 or 2 p.p.m. Se in the diet from the high-selenium garlic produced a 56% or 75% reduction respectively in the total tumor yield. Since both garlic and onion belong to the same allium family of vegetables, we were also interested in finding out whether our experience with garlic could be similarly applied to onion. A high-selenium onion crop was grown in the same season and location and with the same schedule of selenium fertilization. Two distinct differences were noted with the high-selenium onion regarding its capacity to accumulate selenium and its efficacy in cancer prevention. First, the selenium concentration in onion was considerably lower (28 p.p.m. Se dry wt) as compared to that found in garlic (110-150 p.p.m. Se). Second, given the same levels of selenium supplementation, the high-selenium onion was apparently not as powerful as the high-selenium garlic in mammary cancer inhibition. Thus different plants, even those of the same genus, may respond in their unique way to selenium fertilization and the biological benefits of selenium enrichment may vary depending on the species. Additional information from our study indicated that the high-selenium garlic/onion might provide an ideal system for delivering selenium-substituted analogs in a food form for cancer prevention: (i) they expressed a good range of anticancer activity and could be easily adapted for human consumption on a regular basis; (ii) their ingestion did not result in an excessive accumulation of tissue selenium, a concern that is associated with the standard selenium compounds such as selenite and selenomethionine; (iii) no perturbation in the maintenance of functional selenoenzymes were observed even at high levels of supplementation.

Mercury content of small pan fish from New York State waters.

Yellow perch (Perca flavescens) and pumpkin seed (Lepomis gibbosus) were sampled from 16 waters in New York-State and analyzed for total mercury concentration. The levels of mercury in the fish were all well below the safe guideline for human consumption (1 ppm of mercury, fresh weight) of the U.S. Food and Drug Administration. Factors affecting the mobility, methylation and absorption of mercury by fish are discussed.

Residues of p,p'-DDE in lake trout in Little Moose Lake in New York State.

Residues of p,p'-DDE were found in lake trout sampled in 1993 from Little Moose Lake located remotely in the Adirondack region of New York State. Length accounted for 81% of the variation in p,p'-DDE concentration when the data was fit to an exponential model. The presence of p,p'-DDE in the fish was believed due to its long persistence in the aquatic environment following applications of DDT in the 1950s for control of black flies and mosquitoes.

Characterization of tissue selenium profiles and anticarcinogenic responses in rats fed natural sources of selenium-rich products.

The present report describes the biological effects associated with the feeding of three selenium-rich natural products in rats: high-selenium garlic, high-selenium onion and Brazil nut. The first two are experimental crops cultivated with selenium fertilization. Brazil nut is probably the only unadulterated high-selenium food that is available commercially. Tissue selenium profiles, liver glutathione concentrations and mammary cancer inhibition (in the dimethylbenz[a] anthracene model) were the endpoints of investigation. Parallel designs were set up to compare the three high-selenium products with selenite and selenomethionine. Previous studies have shown that treatment with seleno-methionine resulted in significantly greater tissue selenium accumulation, particularly in skeletal muscle, than treatment with selenite. In contrast, selenite, but not selenomethionine, induced a modest increase in liver glutathione concentrations. The objective was to determine whether the high-selenium natural products elicited responses that were similar to that of selenite or selenomethionine. Our experiments suggested that the high-selenium garlic and onion might have some unique attributes. First, their ingestion did not lead to an exaggerated accumulation of tissue selenium, a concern that was shared by both selenomethionine and Brazil nut. Second, unlike selenite, they did not cause any perturbation in glutathione homeostasis. Third, they expressed good anticancer activity that was equal to, if not better than, that of selenite. The chemical form(s) of selenium present in the high-selenium Allium vegetables will be discussed in relation to the manifestation of the above characteristics.