TOXICOLOGICAL SCIENCES 101(1), 22–31 (2008) :::::: Powered by: www.webtar.hu ::::::

<html xmlns:o="urn:schemas-microsoft-com:office:office" xmlns:w="urn:schemas-microsoft-com:office:word" xmlns:st1="urn:schemas-microsoft-com:office:smarttags" xmlns="http://www.w3.org/TR/REC-html40"> <link rel=File-List href="index_files/filelist.xml"> <o:SmartTagType namespaceuri="urn:schemas-microsoft-com:office:smarttags" name="PostalCode"/> <o:SmartTagType namespaceuri="urn:schemas-microsoft-com:office:smarttags" name="date"/> <o:SmartTagType namespaceuri="urn:schemas-microsoft-com:office:smarttags" name="PlaceType"/> <o:SmartTagType namespaceuri="urn:schemas-microsoft-com:office:smarttags" name="PlaceName"/> <o:SmartTagType namespaceuri="urn:schemas-microsoft-com:office:smarttags" name="country-region"/> <o:SmartTagType namespaceuri="urn:schemas-microsoft-com:office:smarttags" name="State"/> <o:SmartTagType namespaceuri="urn:schemas-microsoft-com:office:smarttags" name="City"/> <o:SmartTagType namespaceuri="urn:schemas-microsoft-com:office:smarttags" name="place"/>  <style>  </style>  <body lang=EN-US style='tab-interval:36.0pt'> <div class=Section1> <p class=MsoPlainText>TOX </p> <p class=MsoPlainText><o:p> </o:p></p> <p class=MsoPlainText>Animal studies have demonstrated that the liver is the major target organ of Se toxicity (Diskin et al., 1979). In the present study, we found both Se forms caused liver injury, but SeMSC was more potent as evidenced by serum levels of ALT, AST, and LDH (Figs. 2A–C; Table 4) and the changes of liver architecture (Figs. 4B–D). Moreover, an oral dose of 5 mg Se/ kg for 7 days, SeMSC caused 20% mice death and suppressed mice growth earlier than Nano-Se (Fig. 4A); an oral dose of 10 mg Se/kg for 7 days, SeMSC and Nano-Se caused 80% and 10% mice death, respectively (Fig. 3). In addition, Nano-Se was 6-fold higher in LD50 value than SeMSC (Table 2). The mechanism for the toxic effects of Se has been suggested to occur due to its prooxidant ability to catalyze the oxidation of thiols and simultaneous generation of reactive oxygen species </p> <p class=MsoPlainText><o:p> </o:p></p> <p class=MsoPlainText>(ROS), which can damage cellular components by lipid <span class=GramE>peroxidation(</span>Spallholz,1994).MDAistheproductoflipidperoxidation caused by ROS. Both Se forms caused MDA increase, but its accumulation and duration in liver tissues of SeMSC-treated mice </p> <p class=MsoPlainText><span class=GramE>was</span> higher and longer than that for Nano-Se (Fig. 2D) which implied the extent of oxidative stress was different. In parallel to this, T-AOC, a sum of the activities of the various antioxidative substances, is significantly decreased by SeMSC but not by Nano-Se (Fig. 2F and Table 4); GST, responsible for detoxifying harmful compounds and scavenging lipid peroxidation (Hayes et al., 2005), was induced much earlier and higher by Nano-Se as compared with SeMSC (Fig. 2E and Table 4). </p> <p class=MsoPlainText>Empiric deduction suggests that Nano-Se has an impaired bioavailability due to the decrease in toxicity, especially to its </p> <p class=MsoPlainText><span class=GramE>background</span> of elemental Se, which has long been thought to be biologically inert. Therefore, a comparison of bioavailability was conducted by orally administering SeMSC and Nano-Se to Se-deficient mice once daily for 7 consecutive days. Our results herein showed that the investigated Se forms were equally able to increase GPx and TrxR (Fig. 6). </p> <p class=MsoPlainText>At nutritional levels of Se intake, Se accumulation was comparably efficient between the two Se forms (Fig. 5); however, at a supranutritional level the Se accumulation associated with Nano-Se was significantly lower compared with SeMSC in addition to plasma (Fig. 5). The Se species accumulated from SeMSC at supranutritional level may include methylselenol, an assumed reactive Se species involved in the anticarcinogenic effects of Se (Itoh and Suzuki, 1997). Multiple studies have demonstrated the ability of methylselenol to affect the cell cycle and induce apoptosis in cancer cell lines (Kim <span class=GramE>et</span> </p> <p class=MsoPlainText>al., 2001; <st1:City><st1:place>Medina</st1:place></st1:City> <span class=GramE>et</span> </p> <p class=MsoPlainText><span class=GramE>al., 2001).</span> Therefore, the potential higher accumulation of methylselenol by SeMSC at supranutritional level may lead to argue for its advantage over Nano-Se for chemoprevention. Although the actual chemopreventive mechanisms of Se are still not fully understood, selenoenzymes, phase 2 enzymes, and the cytotoxic effect of Se are all likely to be involved. Therefore, the presumed advantage of SeMSC over Nano-Se is largely dependent on the assumption of a selective modulation of cancer cells by Se and <span class=GramE>a predominant position occupied by cytotoxic pathway over other mechanistic pathways, such as selenoenzymes and phase</span> 2 enzymes. </p> <p class=MsoPlainText><o:p> </o:p></p> <p class=MsoPlainText><span class=GramE>Effect of SeMSC and Nano-Se on GST activity.</span> Se-deficient mice were orally administered SeMSC and Nano-Se at the dose of 500, 1000, and 1500 lg Se/kg once daily for 7 consecutive days. <span class=GramE>Activity of ALT in serum (A).</span> <span class=GramE>Activity of AST in serum (B).</span> <span class=GramE>Activity of GST in liver (C).</span> </p> <p class=MsoPlainText><o:p> </o:p></p> <p class=MsoPlainText><o:p> </o:p></p> <p class=MsoPlainText>ZHANG, WANG, AND XU </p> <p class=MsoPlainText><o:p> </o:p></p> <p class=MsoPlainText>Regarding selectivity, several investigators have reported that Se compounds preferentially inhibit growth and induce apoptosis in cancer cells compared with normal cells (Ghose </p> <p class=MsoPlainText><span class=GramE>et</span> </p> <p class=MsoPlainText>al., 2001; Watrach <span class=GramE>et</span> </p> <p class=MsoPlainText><span class=GramE>al., 1984).</span> However, surprisingly, in the case of liver, the major target of Se toxicity in animals (Diskin et al., 1979), it was found that the cytotoxic effect of Se was at least equally or even more potent in normal hepatocytes compared with hepatic carcinoma cells (Weiller et al., 2004). Consistent with this study, in the case of prostate, an extensively investigated tissue in Se chemoprevention, nontumorigenic prostate cells are highly sensitive to Se toxicity as compared with prostate cancer cells at physiologically relevant concentrations (5–10lM) With respect to the rank of cytotoxic effect among the multiple pathways for chemopreventive effect of Se, to the best of our knowledge, no such a direct comparison has been conducted up to now. On the contrary, in animal studies of Se at supranutritional levels, the modulation of phase 2 enzymes has frequently been reported (El-Sayed et al., 2006; El-Sayed and Franklin, 2006; Ip and Lisk, 1997) and the involvement of selenoenzymes at nutritional levels has again received considerable attention (On the other hand, if the cytotoxic effect of Se is indeed the central mechanism or sole mechanism for its chemopreventive capacity, the risk of Se toxicity seems to be unavoidable unless a superior selectivity to cancer cells is firmly established because ingested supranutritional Se is overwhelmingly taken by normal cells compared with malignant cells in a chemopreventive setting, whereas the converse selectivity, opposite to expectation, that was reported by Weiller et </p> <p class=MsoPlainText><o:p> </o:p></p> <p class=MsoPlainText><span class=GramE>one</span> cannot attribute the predominant chemopreventive mechanism of Se to cytotoxicity alone. In addition, many selenocompounds, such as 1<span class=GramE>,4</span>-phenylenebis(methylene)selenocyanate and 2-substituted selenazolidine-4(R)-carboxylic acids, whose chemical structures are less likely to be metabolized into methylselenol, still possess convincing chemopreventive effects. A prominent profile of these selenocompounds is their capacity to induce phase 2 enzymes in animals at a level lower than the toxic dose (El-Sayed and Franklin, 2006; Sohn et al., 1999). Induction of phase 2 enzymes is an effective and sufficient strategy for achieving protection against the toxic and neoplastic effects of many carcinogens (Talalay, 2000). Therefore, if taking the toxicity of Se into account, the induction of phase 2 response might represent a more attractive mechanism compared with the cytotoxic mechanism. </p> <p class=MsoPlainText><o:p> </o:p></p> <p class=MsoPlainText>Recently, methylselenol precursors were identified to be highly effective selenocompounds for the induction of <span class=GramE>phase <span style='mso-spacerun:yes'> </span>2</span> enzymes in Hepa 1c1c7 cells (Xiao and Parkin, 2006). <span style='mso-spacerun:yes'> </span>It should be noted that the Se level needed for the <span class=GramE>induction <span style='mso-spacerun:yes'> </span>of</span> phase 2 enzymes can be much lower than those causing <span style='mso-spacerun:yes'> </span>cell growth inhibition or cytotoxicity (Xiao and Parkin, <span style='mso-spacerun:yes'> </span>2006). As stated by Xiao and Parkin (2006), methylselenol <span style='mso-spacerun:yes'> </span></p> <p class=MsoPlainText><span class=GramE>precursors</span> were highly effective inducers for phase 2 <span style='mso-spacerun:yes'> </span>response in cells; these authors suggested that animal studies <span style='mso-spacerun:yes'> </span>were needed to assess the gap between effective dose and <span style='mso-spacerun:yes'> </span>toxic dose. Our present study demonstrates that SeMSC <span class=GramE>dose <span style='mso-spacerun:yes'> </span>dependently</span> increases hepatic GST activity at supranutritional <span style='mso-spacerun:yes'> </span>levels (0.5–1.5 mg Se/kg, daily, for 7 days) without <span style='mso-spacerun:yes'> </span>causing toxicity, and that there is no significant difference <span style='mso-spacerun:yes'> </span>between SeMSC and Nano-Se at equi-Se doses (Fig. 7). <span style='mso-spacerun:yes'> </span>However, further escalated doses of SeMSC (5–10 mg Se/kg<span class=GramE>, <span style='mso-spacerun:yes'> </span>daily</span>, for 7 days) produce more prominent toxicity as <span style='mso-spacerun:yes'> </span>compared with Nano-Se. </p> <p class=MsoPlainText><o:p> </o:p></p> <p class=MsoPlainText>Significantly lower accumulation of Se at <span class=GramE>supranutritional <span style='mso-spacerun:yes'> </span>levels</span> in mice fed Nano-Se compared with SeMSC is relevant <span style='mso-spacerun:yes'> </span>to the size effect of Nano-Se and is a strategy for avoiding <span style='mso-spacerun:yes'> </span>toxicity by application of nanotechnology. It has <span class=GramE>been <span style='mso-spacerun:yes'> </span>reported</span> that Nano-Se has a size-dependent effect in <span style='mso-spacerun:yes'> </span>scavenging various free radicals; small-size Nano-Se has <span style='mso-spacerun:yes'> </span>greater ability to transfer electrons to radicals (Huang et <span style='mso-spacerun:yes'> </span>al., <span style='mso-spacerun:yes'> </span>2003). However, the size effect of Nano-Se within 200 nm <span class=GramE>in <span style='mso-spacerun:yes'> </span>terms</span> of induction of selenoenzymes could not be observed <span style='mso-spacerun:yes'> </span>in both Se-deficient cultured cells and Se-deficient mice <span style='mso-spacerun:yes'> </span>at nutritional level (Zhang et <span style='mso-spacerun:yes'> </span>al., 2004). The explanation <span class=GramE>to <span style='mso-spacerun:yes'> </span>this</span> phenomenon has two aspects: intrinsically, an active <span style='mso-spacerun:yes'> </span>absorption pathway as driving force to obtain Se may exist <span style='mso-spacerun:yes'> </span>when Se-deficient cells are thirsty for Se; extrinsically, even <span style='mso-spacerun:yes'> </span>modest Se supplementation can easily saturate selenoenzymes, <span style='mso-spacerun:yes'> </span>thereby excluding a size effect under an urgent need. <span style='mso-spacerun:yes'> </span>At the supranutritional level, in fact, approaching to the <span class=GramE>toxic <span style='mso-spacerun:yes'> </span>level</span>, whereupon selenoenzymes have already been fully <span style='mso-spacerun:yes'> </span>saturated, cells may in turn change to passive absorption of <span style='mso-spacerun:yes'> </span>Se. Our unpublished results which compared Se retention <span class=GramE>of <span style='mso-spacerun:yes'> </span>36</span> and 90 nm Nano-Se at supranutritional levels showed large <span style='mso-spacerun:yes'> </span>size constituted a barrier for Se accumulation. Compared <span class=GramE>with <span style='mso-spacerun:yes'> </span>small</span> molecular weight selenocompounds, for example, <span style='mso-spacerun:yes'> </span>SeMSC herein, 36 nm Nano-Se is fairly larger in size. <span class=GramE>With <span style='mso-spacerun:yes'> </span>respect</span> to Se accumulation, SeMSC and 36 nm Nano-Se did <span style='mso-spacerun:yes'> </span>not show a difference at nutritional levels, but did show <span style='mso-spacerun:yes'> </span>a significant difference at supranutritional levels, which is <span style='mso-spacerun:yes'> </span>exactlythesameastherulesinsizecomparisonbetween36and <span style='mso-spacerun:yes'> </span>90 nm Nano-Se. Reduced accumulation of Se at supranutritional <span style='mso-spacerun:yes'> </span>levels may effectively delay the onset and development <span style='mso-spacerun:yes'> </span>of Se toxicity; fortunately, the reduction of Se accumulation <span style='mso-spacerun:yes'> </span>does not lead to attenuate the induction of GST. <span style='mso-spacerun:yes'> </span><span style='mso-spacerun:yes'> </span>In summary, based on chemoprevention-related responses <span class=GramE>in <span style='mso-spacerun:yes'> </span>animals</span>, as compared with SeMSC, Nano-Se possesses equal <span style='mso-spacerun:yes'> </span>efficacy in increasing the activity of GPx, TrxR, and GST, but <span style='mso-spacerun:yes'> </span>has much lower toxicity, suggesting that Nano-Se can serve as <span style='mso-spacerun:yes'> </span>a potential chemopreventive agent with significantly reduced <span style='mso-spacerun:yes'> </span>risk of Se toxicity. <span style='mso-spacerun:yes'> </span><span style='mso-spacerun:yes'> </span>FUNDING </p> <p class=MsoPlainText><o:p> </o:p></p> <p class=MsoPlainText>This work was supported by a grant from University of </p> <p class=MsoPlainText><span class=GramE>Science and Technology of </span><st1:country-region><st1:place><span class=GramE>China</span></st1:place></st1:country-region><span class=GramE> (KY2002).</span> </p> <p class=MsoPlainText><o:p> </o:p></p> <p class=MsoPlainText><o:p> </o:p></p> <p class=MsoPlainText><o:p> </o:p></p> <p class=MsoPlainText><st1:place><st1:City>NANO-Se</st1:City> <st1:State>AS</st1:State></st1:place> A POTENTIAL CHEMOPREVENTIVE AGENT </p> <p class=MsoPlainText><o:p> </o:p></p> <p class=MsoPlainText>ACKNOWLEDGMENTS </p> <p class=MsoPlainText><o:p> </o:p></p> <p class=MsoPlainText>The authors are grateful to Prof. Ethan Will Taylor for his help in </p> <p class=MsoPlainText><span class=GramE>the</span> revision of the manuscript. We also express our thanks to Hua-Li Wang, </p> <p class=MsoPlainText>Dun-geng Peng, Hong-juan Lu, and Gui-Lan He for technical assistance in the </p> <p class=MsoPlainText><span class=GramE>experiments</span>. </p> <p class=MsoPlainText><o:p> </o:p></p> <p class=MsoPlainText>REFERENCES </p> <p class=MsoPlainText><o:p> </o:p></p> <p class=MsoPlainText><span class=GramE>Albrecht, M. A., Evans, C. W., and Raston, C. L. (2006).</span> Green chemistry <span class=GramE>and <span style='mso-spacerun:yes'> </span>the</span> health implications of nanoparticles. <span class=GramE>Green <span style='mso-spacerun:yes'> </span>Chem</span>. <span style='mso-spacerun:yes'> </span>8<span class=GramE>, <span style='mso-spacerun:yes'> </span>417</span>–432. <span style='mso-spacerun:yes'> </span><span style='mso-spacerun:yes'> </span><span class=GramE>Behne, D., and Kyriakopoulos, A. 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Arch. <span style='mso-spacerun:yes'> </span><span class=GramE>Toxicol.</span> <span style='mso-spacerun:yes'> </span>71<span class=GramE>, <span style='mso-spacerun:yes'> </span>461</span>–466. <span style='mso-spacerun:yes'> </span><span class=GramE>Kim, T., Jung, U., Cho, D. Y., and Chung, A. S. (2001).</span> Se-<span class=GramE>methylselenocysteine <span style='mso-spacerun:yes'> </span>induces</span> apoptosis through caspase activation in HL-60 cells. <span style='mso-spacerun:yes'> </span><span class=GramE>Carcinogenesis <span style='mso-spacerun:yes'> </span>22</span>, <span style='mso-spacerun:yes'> </span>559–565. <span style='mso-spacerun:yes'> </span><st1:City><st1:place><span class=GramE>Medina</span></st1:place></st1:City><span class=GramE>, D., Thompson, H., Ganther, H., and Ip, C. (2001).</span> Se-methylselenocysteine: <span style='mso-spacerun:yes'> </span>A new compound for chemoprevention of breast cancer. <span class=GramE>Nutr.</span> <span style='mso-spacerun:yes'> </span><span class=GramE>Cancer <span style='mso-spacerun:yes'> </span>40</span>, <span style='mso-spacerun:yes'> </span>12–17. <span style='mso-spacerun:yes'> </span><span style='mso-spacerun:yes'> </span>Mehlman, <st1:place>I.</st1:place> J., Simon, N. T., Sanders, A. C., Fishbein, M., Olson, J. C., Jr, <span class=GramE>and <span style='mso-spacerun:yes'> </span>Read</span>, R. B. (1975). <span class=GramE>Microbiological methods.</span> Methodology for <span class=GramE>enteropathogenic <span style='mso-spacerun:yes'> </span>Escherichia</span> coli. J. <span style='mso-spacerun:yes'> </span>Assoc. <span style='mso-spacerun:yes'> </span>Off. <span style='mso-spacerun:yes'> </span><span class=GramE>Anal.</span> <span style='mso-spacerun:yes'> </span><span class=GramE>Chem.</span> <span style='mso-spacerun:yes'> </span>58<span class=GramE>, <span style='mso-spacerun:yes'> </span>283</span>–292. <span style='mso-spacerun:yes'> </span><span style='mso-spacerun:yes'> </span><span class=GramE>Ohkawa, H., Ohishi, N., and Yagi, K. (1979).</span> Assay for lipid peroxides <span class=GramE>in <span style='mso-spacerun:yes'> </span>animal</span> tissues by thiobarbituric acid reaction. <span class=GramE>Anal.</span> <span style='mso-spacerun:yes'> </span><span class=GramE>Biochem.</span> <span style='mso-spacerun:yes'> </span>95<span class=GramE>, <span style='mso-spacerun:yes'> </span>351</span>–358. <span style='mso-spacerun:yes'> </span><span style='mso-spacerun:yes'> </span>Ramos-Gomez, M., Kwak, M. K., Dolan, P. M., Itoh, K., Yamamoto, M.<span class=GramE>, <span style='mso-spacerun:yes'> </span>Talalay</span>, P., and Kensler, T. W. (2001). Sensitivity to carcinogenesis is <span class=GramE>increased <span style='mso-spacerun:yes'> </span>and</span> chemoprotective efficacy of enzyme inducers is lost in nrf2 transcription <span style='mso-spacerun:yes'> </span>factor-deficient mice. <span class=GramE>Proc.</span> <span style='mso-spacerun:yes'> </span><span class=GramE>Natl.</span> <span style='mso-spacerun:yes'> </span><span class=GramE>Acad.</span> <span style='mso-spacerun:yes'> </span><span class=GramE>Sci.</span> <span style='mso-spacerun:yes'> </span><st1:country-region><st1:place>U.S.A.</st1:place></st1:country-region> <span style='mso-spacerun:yes'> </span>98<span class=GramE>, <span style='mso-spacerun:yes'> </span>3410</span>–3415. <span style='mso-spacerun:yes'> </span><span style='mso-spacerun:yes'> </span><span class=GramE>Rebsch, C. M., Penna, F. J., and Copeland, P. R. (2006).</span> Selenoprotein <span class=GramE>expression <span style='mso-spacerun:yes'> </span>is</span> regulated at multiple levels in prostate cells. <span class=GramE>Cell <span style='mso-spacerun:yes'> </span>Res</span>. <span style='mso-spacerun:yes'> </span>16<span class=GramE>, <span style='mso-spacerun:yes'> </span>940</span>–948. <span style='mso-spacerun:yes'> </span><span style='mso-spacerun:yes'> </span>Reid, M. E., Stratton, M. S., Lillico, A. J., Fakih, M., Natarajan, R., Clark, L. C.<span class=GramE>, <span style='mso-spacerun:yes'> </span>and</span> Marshall, J. R. (2004). A report of high-dose selenium supplementation: <span style='mso-spacerun:yes'> </span>Response and toxicities. J. <span style='mso-spacerun:yes'> </span><span class=GramE>Trace <span style='mso-spacerun:yes'> </span>Elem</span>. <span style='mso-spacerun:yes'> </span><span class=GramE>Med.</span> <span style='mso-spacerun:yes'> </span><span class=GramE>Biol.</span> <span style='mso-spacerun:yes'> </span>18<span class=GramE>, <span style='mso-spacerun:yes'> </span>69</span>–74. <span style='mso-spacerun:yes'> </span><span style='mso-spacerun:yes'> </span><span class=GramE>Rodriguez-Lazcano, Y., Pena, Y., Nair, M. T. S., and Nair, P. K. (2005).</span> <span style='mso-spacerun:yes'> </span>Polycrystalline thin films of antimony selenide via chemical bath <span class=GramE>deposition <span style='mso-spacerun:yes'> </span>and</span> post deposition treatments. <span class=GramE>Thin <span style='mso-spacerun:yes'> </span>Solid</span> <span style='mso-spacerun:yes'> </span>Films <span style='mso-spacerun:yes'> </span>493, <span style='mso-spacerun:yes'> </span>77–82. <span style='mso-spacerun:yes'> </span><span style='mso-spacerun:yes'> </span>Rotruck, J. T., Pope, A. L., Ganther, H. E., Swanson, A. B., Hafeman, D. G., <span style='mso-spacerun:yes'> </span>and Hoekstra, W. G. (1973). Selenium: Biochemical role as a component <span class=GramE>of <span style='mso-spacerun:yes'> </span>glutathione</span> peroxidase. <span class=GramE>Science <span style='mso-spacerun:yes'> </span>179</span>, <span style='mso-spacerun:yes'> </span>588–590. <span style='mso-spacerun:yes'> </span><span style='mso-spacerun:yes'> </span><span class=GramE>Sohn, O. S., Fiala, E. S., Upadhyaya, P., Chae, Y. H., and El-Bayoumy, K.</span> <span style='mso-spacerun:yes'> </span>(1999). Comparative effects of <span class=GramE>phenylenebis(</span>methylene)selenocyanate <span style='mso-spacerun:yes'> </span>isomers on xenobiotic metabolizing enzymes in organs of female CD rats. <span style='mso-spacerun:yes'> </span><span class=GramE>Carcinogenesis <span style='mso-spacerun:yes'> </span>20</span>, <span style='mso-spacerun:yes'> </span>615–621. <span style='mso-spacerun:yes'> </span><span style='mso-spacerun:yes'> </span>Spallholz, J. E. (1994). On the nature of selenium toxicity and <span class=GramE>carcinostatic <span style='mso-spacerun:yes'> </span>activity</span>. <span class=GramE>Free <span style='mso-spacerun:yes'> </span>Radic</span>. <span style='mso-spacerun:yes'> </span><span class=GramE>Biol.</span> <span style='mso-spacerun:yes'> </span><span class=GramE>Med.</span> <span style='mso-spacerun:yes'> </span>17<span class=GramE>, <span style='mso-spacerun:yes'> </span>45</span>–64. <span style='mso-spacerun:yes'> </span><span style='mso-spacerun:yes'> </span><span class=GramE>Sty´blo, M., Kalouskova´, J., and Klas, J. (1991).</span> Comparison of the kinetics <span class=GramE>of <span style='mso-spacerun:yes'> </span>a</span> trace and a sublethal dose of selenite in rats, with particular attention being <span style='mso-spacerun:yes'> </span>given to blood selenium distribution. J. <span style='mso-spacerun:yes'> </span><span class=GramE>Trace <span style='mso-spacerun:yes'> </span>Elem</span>. <span style='mso-spacerun:yes'> </span><span class=GramE>Electrolytes <span style='mso-spacerun:yes'> </span>Health</span> <span style='mso-spacerun:yes'> </span>Dis. <span style='mso-spacerun:yes'> </span>5<span class=GramE>, <span style='mso-spacerun:yes'> </span>155</span>–164. <span style='mso-spacerun:yes'> </span><span style='mso-spacerun:yes'> </span><span class=GramE>Sty´blo, M., Kalouskova´, J., and Pavli´k, L. (1988).</span> Dose-dependent <span class=GramE>distribution <span style='mso-spacerun:yes'> </span>of</span> injected selenium in rat blood. Effect of previous selenium intake <span class=GramE>in <span style='mso-spacerun:yes'> </span>drinking</span> water. 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(2007).</span> Elemental selenium at nano <span class=GramE>size <span style='mso-spacerun:yes'> </span>possesses</span> lower toxicity without compromising the fundamental effect on <span style='mso-spacerun:yes'> </span>selenoenzymes: Comparison with selenomethionine in mice. <span class=GramE>Free <span style='mso-spacerun:yes'> </span>Radic</span>. <span style='mso-spacerun:yes'> </span><span class=GramE>Biol.</span> <span style='mso-spacerun:yes'> </span><span class=GramE>Med.</span> <span style='mso-spacerun:yes'> </span>42<span class=GramE>, <span style='mso-spacerun:yes'> </span>1524</span>–1533. <span style='mso-spacerun:yes'> </span><span style='mso-spacerun:yes'> </span><span class=GramE>Watrach, A. M., Milner, J. A., Watrach, M. A., and Poirier, K. A. (1984).</span> <span style='mso-spacerun:yes'> </span>Inhibition of human breast cancer cells by selenium. <span class=GramE>Cancer <span style='mso-spacerun:yes'> </span>Lett</span>. <span style='mso-spacerun:yes'> </span>25<span class=GramE>, <span style='mso-spacerun:yes'> </span>41</span>–47. <span style='mso-spacerun:yes'> </span><span style='mso-spacerun:yes'> </span><span class=GramE>Weiller, M., Latta, M., Kresse, M., Lucas, R., and Wendel, A. (2004).</span> <span class=GramE>Toxicity <span style='mso-spacerun:yes'> </span>of</span> nutritionally available selenium compounds in primary and transformed <span style='mso-spacerun:yes'> </span>hepatocytes. <span class=GramE>Toxicology <span style='mso-spacerun:yes'> </span>201</span>, <span style='mso-spacerun:yes'> </span>21–30. <span style='mso-spacerun:yes'> </span><span style='mso-spacerun:yes'> </span><span class=GramE>Whanger, P. D. (2004).</span> Selenium and its relationship to cancer: An <span class=GramE>update <span style='mso-spacerun:yes'> </span>dagger</span>. <st1:country-region><st1:place>Br.</st1:place></st1:country-region> <span style='mso-spacerun:yes'> </span>J. <span style='mso-spacerun:yes'> </span>Nutr. <span style='mso-spacerun:yes'> </span>91<span class=GramE>, <span style='mso-spacerun:yes'> </span>11</span>–28. <span style='mso-spacerun:yes'> </span><span style='mso-spacerun:yes'> </span><span class=GramE>Xiao, H., and Parkin, K. L. (2006).</span> Induction of phase II enzyme activity <span class=GramE>by <span style='mso-spacerun:yes'> </span>various</span> selenium compounds. <span class=GramE>Nutr.</span> <span style='mso-spacerun:yes'> </span><span class=GramE>Cancer <span style='mso-spacerun:yes'> </span>55</span>, <span style='mso-spacerun:yes'> </span>210–223. <span style='mso-spacerun:yes'> </span><span style='mso-spacerun:yes'> </span>Zhang, J., Svehlikova, V., Bao, Y., Howie, A. F., Beckett, G. J., <span class=GramE>and <span style='mso-spacerun:yes'> </span>Williamson</span>, G. (2003). Synergy between sulforaphane and selenium in <span class=GramE>the <span style='mso-spacerun:yes'> </span>induction</span> of thioredoxin reductase 1 requires both transcriptional and <span style='mso-spacerun:yes'> </span>translational modulation. <span class=GramE>Carcinogenesis <span style='mso-spacerun:yes'> </span>24</span>, <span style='mso-spacerun:yes'> </span>497–503. <span style='mso-spacerun:yes'> </span><span style='mso-spacerun:yes'> </span><span class=GramE>Zhang, J., Wang, H., Bao, Y., and Zhang, L. (2004).</span> Nano red <span class=GramE>elemental <span style='mso-spacerun:yes'> </span>selenium</span> has no size effect in the induction of seleno-enzymes in both <span style='mso-spacerun:yes'> </span>cultured cells and mice. <span class=GramE>Life <span style='mso-spacerun:yes'> </span>Sci</span>. <span style='mso-spacerun:yes'> </span>75<span class=GramE>, <span style='mso-spacerun:yes'> </span>237</span>–244. <span style='mso-spacerun:yes'> </span><span style='mso-spacerun:yes'> </span><span class=GramE>Zhang, J., Wang, H., Yan, X., and Zhang, L. (2005).</span> Comparison of short-<span class=GramE>term <span style='mso-spacerun:yes'> </span>toxicity</span> between Nano-Se and selenite in mice. <span class=GramE>Life <span style='mso-spacerun:yes'> </span>Sci</span>. <span style='mso-spacerun:yes'> </span>76<span class=GramE>, <span style='mso-spacerun:yes'> </span>1099</span>–1109. <span style='mso-spacerun:yes'> </span><span style='mso-spacerun:yes'> </span>Zhang, J. S., <span class=GramE>Gao</span>, X. Y., Zhang, L. D., and Bao, Y. P. (2001). <span class=GramE>Biological <span style='mso-spacerun:yes'> </span>effects</span> of a nano red elemental selenium. <span class=GramE>Biofactors <span style='mso-spacerun:yes'> </span>15</span>, <span style='mso-spacerun:yes'> </span>27–38. <span style='mso-spacerun:yes'> </span><span style='mso-spacerun:yes'> </span><span style='mso-spacerun:yes'> </span><span style='mso-spacerun:yes'> </span>JOURNAL <span style='mso-spacerun:yes'> </span>OF Inorganic Biochemistry <span style='mso-spacerun:yes'> </span><span style='mso-spacerun:yes'> </span>Journal of Inorganic Biochemistry 101 (2007) 1457–1463 <span style='mso-spacerun:yes'> </span><span style='mso-spacerun:yes'> </span>www.elsevier.com/locate/jinorgbio <span style='mso-spacerun:yes'> </span><span style='mso-spacerun:yes'> </span>Size effect of elemental selenium nanoparticles (Nano-Se) at supranutritional levels on selenium accumulation and glutathione S-transferase activity <span style='mso-spacerun:yes'> </span><span style='mso-spacerun:yes'> </span>Dungeng Peng a, Jinsong Zhang a,*, Qingliang Liu a, Ethan Will Taylor b a School of Chemistry and Materials of Science, University of Science and Technology of China, Hefei 230052, Anhui, PR China <span style='mso-spacerun:yes'> </span>b Laboratory for Molecular Medicine, Office of Research, 206 Eberhart Bldg., <st1:place><st1:PlaceType>University</st1:PlaceType> of <st1:PlaceName>North Carolina</st1:PlaceName></st1:place> at <st1:City><st1:place>Greensboro</st1:place></st1:City>, <span style='mso-spacerun:yes'> </span><st1:place><st1:City>Greensboro</st1:City>, <st1:State>NC</st1:State> <st1:PostalCode>27402-6170</st1:PostalCode>, <st1:country-region>United States</st1:country-region></st1:place> <span style='mso-spacerun:yes'> </span><span style='mso-spacerun:yes'> </span>Received <st1:date Year="2007" Day="22" Month="3">22 March 2007</st1:date>; received in revised form <st1:date Year="2007" Day="14" Month="6">14 June 2007</st1:date>; accepted 18 June 2007 Available online 27 June 2007 <span style='mso-spacerun:yes'> </span><span style='mso-spacerun:yes'> </span></p> </div> </body> <br>Partneroldalak: <br> <a href="http://domain.domainshop.hu/domain.html" alt="tárhely domainregisztráció">Domain regisztráció tár és szerverszolgáltatások: domain domainnév tárhely e-mail, imap, pop3</a><br> <a href="http://www.webtar.hu" alt="tárhely donainregisztráció">www.webtar.hu</a><br> <a href="http://www.micropay.hu" alt="micropay">www.micropay.hu</a><br> <a href="http://www.ingyenweb.hu" alt="ingyenweb">www.ingyenweb.hu</a><br> <a href="http://www.videok.hu" alt="Videók">www.videok.hu</a><br> <a href="http://www.xn--antikvrium-x4a.hu" alt="Antikvárium">www.antikvárium.hu</a><br> <a href="http://www.ftpdir.hu" alt="ftpdir">www.ftpdir.hu</a><br> <a href="http://xn--fotk-sqa.hu" alt="fotók">www.fotók.hu</a><br> <a href="http://www.randi.hu" alt="Randi">www.randi.hu</a><br> <a href="http://www.licit.hu" alt="Licit">www.licit.hu</a><br> <a href="http://www.napivicc.hu" alt="vicc">www.napivicc.hu</a><br> <a href="http://www.gyertyalang.hu" alt="gyertyagyújtás">www.gyertyalang.hu</a><br> <a href="http://www.xn--helyesrs-fza2j.hu" alt="helyesírás.hu">www.helyesírás.hu</a><br> <a href="http://domain.webtar.hu/domain.html" alt="Domain regiszráció és tárhely">Domain regisztráció</a><br>