Sepp1 in situ hybridization of a lactating mouse mammary gland.

<p>Sepp1 mRNA is indicated by blue staining. Panel A was stained using the antisense Sepp1 riboprobe and panel B was stained using the sense Sepp1 riboprobe.</p

Effects of selenium intake and selenoprotein genotype of the dam on neonate selenium retention from milk.

<p>The experiments shown in each panel were carried out separately. Neonate whole-body selenium values depicted are means with S.D. indicated by a half bracket, n = 18–41. Dam genotypes and diet selenium supplements are shown in the lower half of the figure. Dams with gene deletions had been mated with C57BL/6 males, yielding neonates that were all heterozygous for the respective gene. Neonates were removed from the dam at day 1 or day 5 of life. They were weighed and euthanized and then assayed for selenium. The values in this figure were calculated from the raw data in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0103486#pone.0103486.s002" target="_blank">Table S1</a>. Weight gain and selenium gain over the 4 days are shown in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0103486#pone-0103486-t001" target="_blank">Table 1</a>.</p

Selenium-containing proteins in milk whey detected by autoradiogram of an SDS-PAGE gel.

<p>Panel A is the autoradiogram of the gel and panel B depicts the gel stained by Coomassie blue. Dams that had been lactating 10–16 d were milked 24 h after administration of a tracer dose of ⁷⁵SeO₃²⁻ and the whey fraction of the milk was subjected to SDS-PAGE. ⁷⁵Se-labeled plasma was included as a control. After drying, the gel was exposed to x-ray film. Lane 1 represents plasma (0.5 µl and 321 cpm applied) and lanes 2–5 represent whey (lane 2–1.5 µl and 260 cpm applied; lane 3–2 µl and 124 cpm applied; lane 4–1 µl and 288 cpm applied; lane 5–2 µl and 162 cpm applied). Deletion of selenoprotein genes in the dams is indicated in the lower half of the figure.</p

Effects of selenoprotein genotypes on milk selenium concentration.

<p>Panel A shows the effect of <i>Sepp1</i> deletion and panel B shows the effect of <i>Gpx3</i> deletion. Dam selenoprotein genotype is indicated below the graphs. All dams were fed diet supplemented with 0.25 mg selenium/kg. Values are means with 1 S.D. indicated by the half bracket, n = 4–9. The asterisk indicates that the two bars are significantly different by Student’s <i>t-</i>test, p<0.001. The n.s. designation indicates that the two bars are not significantly different by the same test. See <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0103486#pone.0103486.s003" target="_blank">Table S2</a> for supporting data.</p

Effect of dam genotype on nursing pup weight gain and selenium acquisition from day 1 to day 5 of life^a.

a<p>See <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0103486#pone.0103486.s002" target="_blank">Table S1</a> for supporting data.</p>b<p>Values are means ± 1 S.D.</p>c<p>Values were calculated using day 1 and day 5 means.</p

Gpx3 in situ hybridization of a lactating mouse mammary gland.

<p>Gpx3 mRNA was stained blue. Panel A was stained using the antisense Gpx3 riboprobe and panel B was stained using the sense Gpx3 riboprobe. See <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0103486#pone.0103486.s001" target="_blank">Figure S1</a> for a positive control.</p

Plasma selenium concentration odds ratios for black and white Americans participating in the SCCS.

<p>SEPP1 - Selenoprotein P; GPX3 - Glutathione Peroxidase</p><p>†Quartile cutpoints were based on the distribution for each selenium (Se) plasma concentration with whites and blacks combined.</p><p>‡All models were adjusted for gender, age, education, household income, body mass index, smoking status, fruit and vegetable intake, meat and fish intake, and living on farm.</p

Mean difference by sociodemographic and lifestyle variables for selenium biomarkers among SCCS participants.

<p>BMI - Body Mass Index; SEPP1 - Selenoprotein P; GPX3 - Glutathione Peroxidase.</p

Comparison of plasma selenium concentration between the SCCS and NHANES III (1988–1994) participants.

<p>NHANES III: 40–79 yrs, South region of US.; BMI - Body Mass Index.</p

Dietary Selenium Deficiency Exacerbates DSS-Induced Epithelial Injury and AOM/DSS-Induced Tumorigenesis

<div><p>Selenium (Se) is an essential micronutrient that exerts its functions via selenoproteins. Little is known about the role of Se in inflammatory bowel disease (IBD). Epidemiological studies have inversely correlated nutritional Se status with IBD severity and colon cancer risk. Moreover, molecular studies have revealed that Se deficiency activates WNT signaling, a pathway essential to intestinal stem cell programs and pivotal to injury recovery processes in IBD that is also activated in inflammatory neoplastic transformation. In order to better understand the role of Se in epithelial injury and tumorigenesis resulting from inflammatory stimuli, we examined colonic phenotypes in Se-deficient or -sufficient mice in response to dextran sodium sulfate (DSS)-induced colitis, and azoxymethane (AOM) followed by cyclical administration of DSS, respectively. In response to DSS alone, Se-deficient mice demonstrated increased morbidity, weight loss, stool scores, and colonic injury with a concomitant increase in DNA damage and increases in inflammation-related cytokines. As there was an increase in DNA damage as well as expression of several EGF and TGF-β pathway genes in response to inflammatory injury, we sought to determine if tumorigenesis was altered in the setting of inflammatory carcinogenesis. Se-deficient mice subjected to AOM/DSS treatment to model colitis-associated cancer (CAC) had increased tumor number, though not size, as well as increased incidence of high grade dysplasia. This increase in tumor initiation was likely due to a general increase in colonic DNA damage, as increased 8-OHdG staining was seen in Se-deficient tumors and adjacent, non-tumor mucosa. Taken together, our results indicate that Se deficiency worsens experimental colitis and promotes tumor development and progression in inflammatory carcinogenesis.</p></div