Pendrin mediates uptake of perchlorate in a mammalian in vitro system

Perchlorate is a known endocrine disruptor present in groundwater, vegetables and dairy food products in many regions of the United States. It interferes with the uptake of iodide into the thyrocyte by the sodium-iodide symporter at the basolateral surface, thus potentially disrupting the synthesis of thyroid hormone. Because transport of iodide from the thyroid follicular cells to the follicular lumen is mediated by the protein pendrin at the apical surface, we hypothesized that perchlorate may also interact with this protein. Therefore, HeLa cells were transfected with the human SLC26A4 gene, which encodes pendrin, to generate an in vitro mammalian system expressing the recombinant pendrin protein (HeLa-PDS). The HeLa-PDS cells, along with untransfected cells, were then cultured in presence of iodide and/or perchlorate. Intracellular levels of these two chemicals were measured by ion chromatography tandem mass spectrometry. Results from this study show that iodide and perchlorate uptake increases significantly in HeLa-PDS cells as compared to untransfected cells. Thus, recombinant HeLa cells expressing pendrin protein accumulate iodide and perchlorate intracellularly, indicating that pendrin is involved in the uptake of perchlorate. Additional results from this study suggest that iodide and perchlorate competitively inhibit each other for uptake by pendrin. The ability of perchlorate to compete with iodide for uptake by both basal and apical transporters may increase the potential of perturbation of thyroid homeostasis and therefore the estimated risk posed to susceptible human populations.     

Effect of Nonylphenol on Steroidogenesis of Rat Leydig Cells

Nonylphenol is the primary final biodegradation product of nonylphenol polyethoxylate (NPE), a non-ionic surfactant that is frequently incorporated into pesticide and detergent formulation. Recent researchers have hypothesized that environmental/ occupational exposure to nonylphenol poses adverse effects on reproductive system of humans and wildlife species. During our study, in vivo and in vitro experiments were performed to examine the effect of nonylphenol on testosterone biosynthesis of rat Leydig cells. In experiment in vivo, serum testosterone (T) as well as luteinizing hormone (LH) levels were detected after animals had been treated with different doses (0 mg/kg/day, 125 mg/kg/day, and 250 mg/kg/day) of nonylphenol for 50 days by gavage, and the final result revealed that testosterone level dramatically declined at the dose of 250 mg/kg/day, while LH level ascended at the dose of 125 mg/kg/day and 250 mg/kg/day. In experiment in vitro, primary cultured Leydig cells were exposed to nonylphenol for 48 h, including low concentrations (0 mg/L, 0.0011 mg/L, 0.0033 mg/L, 0.0055 mg/L, 0.011 mg/L, 0.022 mg/L) and higher concentrations (0.11 mg/L, 0.55 mg/L, 1.1 mg/L, 1.65 mg/L, 2.2 mg/L, 2.75 mg/L, 3.3 mg/L, 5.5 mg/L). Increase of testosterone levels was observed at low concentrations of nonylphenol while reduction was detected at higher concentrations.     

稀土的hormesis效应及其农用对农业生态环境的潜在影响

毒物刺激效应(hormesis)是指毒物对生物生理过程产生的刺激效应。从稀土元素对生物的刺激效应及其疑似环境激素的问题出发,探讨农业应用稀土对农业生态环境的潜在影响。     

几种激素对光合细菌生长的影响

提出在培养基中添加一定浓度的动物或植物生长激素可促进光合细茵的生长。泼尼松、地塞米松、三十烷醇、α-萘乙酸的最适添加浓度分别为0．5mg／L,1mg/L,0．5mg/L和0．5mg/L。混和激素促生效果好于单一激素。指出在生产性培养中,添加某些激素促进光合细茵的生长是可行的。     

Liquid discharges from patients undergoing I treatments

This work discusses the production and management of liquid radioactive wastes as excretas from patients undergoing therapy procedures with ¹³¹I radiopharmaceuticals in Spain. The activity in the sewage has been estimated with and without waste radioactive decay tanks. Two common therapy procedures have been considered, the thyroid cancer (4.14 GBq administered per treatment), and the hyperthyroidism (414 MBq administered per treatment). The calculations were based on measurements of external exposure around the 244 hyperthyroidism patients and 23 thyroid cancer patients. The estimated direct activity discharged to the sewage for two thyroid carcinomas and three hyperthyroidisms was 14.57 GBq and 1.27 GBq, respectively, per week; the annual doses received by the most exposed individual (sewage worker) were 164 μSv and 13 μSv, respectively. General equations to calculate the activity as a function of the number of patient treated each week were also obtained.     

邻苯二甲酸丁基苄酯的生殖毒性及其作用机制

为评价邻苯二甲酸丁基苄酯在体内的慢性毒性,以1000mg/kg、500mg/kg、250mg/kg剂量连续染毒大鼠6周、20周.结果表明:邻苯二甲酸丁基苄酯能引起雄鼠睾丸(p＜0.01)、附睾和前列腺重量的减少(p＜0.05)和肝脏肿大(p＜0.01),改变睾丸(p＜0.01)、前列腺(p＜0.05)、肝脏(p＜0.01)的组织病理学,尤其引起睾丸曲细精管萎缩、变性,各级生精细胞减少,生精上皮内生精细胞和Sertoli细胞结构明显紊乱,细胞间连接结构消失.降低血清中γ-G(p＜0.01)、ALP(p＜0.05)活性、睾酮水平(p＜0.01),增加LDH活性(p＜0.01)和FSH水平(p＜0.01),呈一定的量-效和时-效关系.结合组织病理和性激素及酶活性的改变,揭示该化合物睾丸毒性的靶细胞是支持细胞,其次是生精细胞,作用的靶点是细胞内的线粒体.邻苯二甲酸丁基苄酯对雌鼠的损害只引起子宫的增大和轻微炎症表现及血清ALP酶活性的降低(p＜0.05).充分说明了邻苯二甲酸丁基苄酯对动物的干扰有明显的性别差异,对雄性的危害要远远大于对雌性的损害.     

化学农药与环境激素

环境激素是指有可能干扰人与脊椎动物内分泌的外因性化学物质。在已知的６７ 种（或类）环境激素有机物中,化学农药（包括除草剂、杀虫剂、杀菌剂）及其代谢产物共占４４ 种,几近三分之二。在已进行环境调查的４７ 种环境激素中,已检出的有２４ 种,占二分之一。列举了环境激素对人类和动物生育、生理功能的影响,并指出研制开发“安全化学农药”的思路是不可取的。     

Optimization of the T3-induced Xenopus metamorphosis assay for detecting thyroid hormone signaling disruption of chemicals

T3-induced Xenopus metamorphosis is an ideal model for detecting thyroid hormone(TH)signaling disruption of chemicals. To optimize the T3-induced Xenopus assay and improve its sensitivity and reproducibility, we intend to develop quantitatively morphological endpoints and choose appropriate concentrations and exposure durations for T3 induction.Xenopus laevis at stage 52 were exposed to series of concentrations of T3(0.31–2.5 nmol/L)for 6 days. By comparing morphological changes induced by T3, we propose head area,mouth width, unilateral brain width/brain length, and hindlimb length/snout-vent length as quantitative parameters for characterizing T3-induced morphological changes, with body weight as a parameter for indicating integrated changes. By analyzing time-response curves, we found that following 4-day exposure, T3-induced grossly morphological changes displayed linear concentration–response curves, with moderate morphological changes resulting from 1.25 nmol/L T3 exposure. When using grossly morphological endpoints to detect TH signaling disruption, we propose 4 days as exposure duration of T3, with concentrations close to 1.25 nmol/L as induction concentrations. However, it is appropriate to examine morphological and molecular changes of the intestine on day 2 due to their early response to T3. The quantitative endpoints and T3 induction concentrations and durations we determined would improve the sensitivity and the reproducibility of the T3-induced Xenopus metamorphosis assay.     

Bisphenol A exposure alters release of immune and developmental modulators and expression of estrogen receptors in human fetal lung fibroblasts

Bisphenol A(BPA) has been shown to exert biological effects through estrogen receptor(ER)-dependent and ER-independent mechanisms. Recent studies suggest that prenatal exposure to BPA may increase the risk of childhood asthma. To investigate the underlying mechanisms in the actions of BPA, human fetal lung fibroblasts(h FLFs) were exposed to varying doses of BPA in culture for 24 hr. Effects of BPA on localization and uptake of BPA,cell viability, release of immune and developmental modulators, cellular localization and expression of ERα, ERβ and G-protein coupled estrogen receptor 30(GPR30), and effects of ERs antagonists on BPA-induced changes in endothelin-1(ET-1) release were examined.BPA at 0.01–100 μmol/L caused no changes in cell viability after 24 hr of exposure. h FLFs expresses all three ERs. BPA had no effects on either cellular distribution or protein expression of ERα, however, at 100 μmol/L(or 23 μmol/L intracellular BPA) increased ERβprotein levels in the cytoplasmic fractions and GPR 30 protein levels in the nuclear fractions.These paralleled with increased release of growth differentiation factor-15, decreased phosphorylation of nuclear factor kappa B p65 at serine 536, and decreased release of ET-1,interleukin-6, and interferon gamma-induced protein 10. ERs antagonists had no effects on BPA-induced decrease in ET-1 release. These data suggest that BPA at 100 μmol/L altered the release of immune and developmental modulators in h FLFs, which may negatively influence fetal lung development, maturation, and susceptibility to environmental stressors, although the role of BPA in childhood asthma remains to be confirmed in in vivo studies.     

全氟辛烷基磺酸钾(PFOS)和纳米氧化锌(Nano-ZnO)复合暴露对斑马鱼下丘脑-垂体-甲状腺轴功能的影响

全氟辛烷基磺酸钾(PFOS)和纳米氧化锌(Nano-Zn O)广泛存在于环境中,但是它们复合暴露对水生生物的潜在毒性机制尚未明确。本文探讨PFOS和Nano-Zn O复合暴露对斑马鱼下丘脑-垂体-甲状腺轴(HPT轴)毒性的影响。将斑马鱼胚胎从孵化开始暴露于PFOS(0.2、0.4、0.8 mg·L~(-1))、Nano-Zn O(6.75、12.5、25 mg·L~(-1))、PFOS+Nano-Zn O(0.2+6.75、0.4+12.5、0.8+25 mg·L~(-1))溶液中15 d后,分析幼鱼的发育毒性,体内的甲状腺激素(甲状腺素(T4)和三碘甲状腺氨酸(T3)含量和与甲状腺有关基因(CRF、TSH、NIS、TG和TPO)的表达情况。结果发现复合暴露组与单独暴露组相比,前者显著诱导了幼鱼的畸形率,降低了幼鱼的存活率,并抑制了幼鱼的体长。复合暴露组显著增加了幼鱼体内T3含量,同时抑制体内T4的含量。与单独暴露组相比,复合暴露组显著诱导了CRF和NIS基因的表达,同时抑制了TSHβ和TG基因的表达。而TPO基因的表达水平在单独和复合暴露组中没有显著差异。本研究首次证明了PFOS和Nano-Zn O复合暴露对斑马鱼幼鱼甲状腺轴的干扰效果并对其进行了机制探讨。