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PubMed1976

The inhibitory effect of acute administration of excess iodide on the formation of adenosine 3', 5'-monophosphate induced by thyrotropin in mouse thyroid lobes.

In a previous paper, we demonstrated that an inhibitory action of excess iodide on thyrotropin-induced thyroid hormone secretion occurs at a site subsequent to the generation of cyclic AMP. In the present study, however, we have found that thyroidal cyclic AMP formation induced by thyrotropin in vitro was markedly inhibited by the acute administration of excess iodide to mice fed a low iodine diet. In contrast, excess iodide failed to produce inhibition in animals fed a regular diet. In vitro stimulation by long-acting thyroid stimulator (LATS), prostaglandin E2, and 4-methylhistamine of cyclic AMP formation in mouse thyroid lobes was also significantly inhibited by the acute in vivo administration of excess iodide. The inhibition was completely relieved by the administration of methimazole prior to excess iodide. Furthermore, it has been shown that thyroid adenylate cyclase activity induced by thyrotropin was markedly depressed by excess iodide under similar experimental conditions. Therefore, it is suggested that one of the inhibitory actions of excess iodide is on the adenylate cyclase-cyclic AMP system and further, that iodide can elicit its inhibitory action after its conversion to some form of organic iodine.

Adenylyl Cyclases↗
PubMed1993

Enhancement of thyrotropin-stimulated iodide organification in porcine thyroid cells after protein kinase-C inhibition.

We and others have previously shown that 12-O-tetracanoylphorbol-13-acetate (TPA), a protein kinase-C (PKC) activator, inhibits TSH-stimulated iodide organification in porcine thyroid cells. However, TPA action may be independent of PKC. To further explore the role of PKC in the regulation of differentiated thyroid function, we studied the effects of the PKC inhibitors 1-O-hexadecyl-2-O-methylglycerol (AMG-C16), 1-(5-isoquinolinesulfonyl)2-methylpiperazine (H7), and staurosporine on TSH-stimulated iodide organification in porcine thyroid cells in the presence and absence of TPA. AMG-C16 increased basal iodide organification in concentrations ranging from 15-240 microM (P < 0.01, by analysis of variance). Such stimulation by AMG-C16 (30-120 microM) persisted in the presence of submaximal (10 microU) and maximal (1 mU) concentrations of TSH. However, in the presence of TPA (> 10 nM), the effects of AMG-C16 were abolished. H7 (50 microM) and staurosporine (100 nM) also enhanced TSH-stimulated iodide organification. In the presence of staurosporine and TPA, no inhibition of TSH-stimulated iodide organification was observed. However, H7 could not reverse the effects of TPA. In summary, these studies indicate that in porcine thyroid cells, three distinct PKC inhibitors all enhanced TSH-stimulated iodide organification and that staurosporine reversed the effects of TPA on TSH-stimulated iodide organification. These findings are consistent with the concept that PKC acts as an endogenous negative modulator of iodide organification in vitro.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1996

In vivo and in vitro evidence for iodide regulation of major histocompatibility complex class I and class II expression in Graves' disease.

Increases in thyroid cell major histocompatibility complex (MHC) class I and class II expression have been suggested to be an important factor in the development or perpetuation of Graves' disease. It is hypothesized that elevations result in abnormal presentation of thyroid antigens to immune cells, and that iodide and/or methimazole (MMI) are effective therapeutic agents because, at least in part, of their suppression of MHC expression. In this report, we show that Graves' patients pretreated with iodide only 4 days before surgery have lower levels of MHC class I and class II RNA levels in their thyroid tissue than do patients with no iodide pretreatment (P < 0.001 and 0.03, respectively). Because patients in both groups are treated with MMI and because the change is independent of the amounts of MMI used to treat patients, the class I and class II changes cannot be ascribed to MMI. The iodide action to decrease MHC class I and class II RNA levels was duplicated using cultured human thyroid cells in vitro; the iodide effect was dependent on the iodide concentration, was not duplicated by chloride, was not associated with an alteration in cAMP levels or with a change in thyrotropin receptor RNA levels, and was evident in gamma-interferon-treated cells. The data suggest, therefore, that the therapeutic action of iodide in Graves' patients is associated with decreased MHC gene expression, that this action is a direct effect of high concentrations of iodide on the thyroid cells, and that altered MHC gene expression in the target tissue may well be associated with the development or perpetuation of Graves' disease.

Adolescent↗
PubMed1976

Studies on proteolytic activity and function of the thyroid gland in rats administered excess iodide.

Thyroid auto-proteolytic activity in rats increased significantly only after several weeks of treatment with 1 mg iodide per day. Iodide added in vitro did not activate thyroid auto-proteolysis, nor was inhibition observed. Thyroid proteolytic activity was also tested using 131I-labelled heat-inactivated thyroid homogenate from control rats as substrate. Significantly increased proteolytic activity was again demonstrated in thyroid glands from rats on excess iodide for several weeks. The increased proteolytic activity is therefore probably not due to a decreased proteolytic resistance of thyroglobulin in the iodide-treated rats. Increased synthesis or decreased degradation of thyroid proteolytic enzymes is a more likely explanation for this phenomenon. These findings are at variance with those of some previous studies showing decreased proteolytic activity in thyroid glands from rats administered excess iodide. Since the rats remained euthyroid the increased auto-proteolysis, which occurred quite late, was considered an unexpected finding and it is at present not certain whether this is related to the successful adaptation. Treatment with iodide did not alter the thyroid and hypophyseal weight or histology. Serum free thyroxine level and thyrotropin concentration were also unaffected by excess iodide. The adaptation of the imtact rat thyroid to prolonged and excess iodide intake seems to occur without the assistance of an altered thyrotrophin secretion.

Animals↗
PubMed1984

Vascularization and iodide transport down regulation in rat goitre.

This study was designed to investigate, in the rat, the regulation of the amount of thyroid iodide and of its organification during the involution of an experimentally induced goitre. The goitre was obtained by drastic iodine deficiency; male Wistar rats received an iodide deficient diet for 6 months, supplemented with PTU during the last 2 months. The study was followed for 16 days after the beginning of iodide refeeding (daily iodine intake = 50 micrograms). The thyroid iodide, total thyroid organic iodine and plasma iodide, PBI and TSH concentrations were determined from day 0 to 16 and compared to their control values (rats on a normal iodide diet for 6 months). In addition, a stereological study was carried out to determine if the extent of the gland vasculature might be implicated in the regulation of the thyroid iodide content. The plasma TSH concentration was very high and constant for 8 days (2.40 +/- 0.37 and 2.45 +/- 0.43 on day 0 and 8 respectively vs 0.25 +/- 0.12 microgram/ml in control rats), whereas iodination and secretion were blocked for 4 days (0.34 +/- 0.19 and 0.5 +/- 0.1 on day 0 and 4 respectively vs 14.4 +/- 2.0 micrograms 127I/gland in control rats) (Wolff-Chaikoff effect). Thyroid iodide amount increased enormously for 2 days (2.5 +/- 0.6 and 2.45 +/- 0.55 respectively on day 1 and 2 vs 0.09 +/- 0.01 micrograms 127I/gland on day 0), then strongly decreased between 2 and 4 days (1.15 +/- 0.27 127I/gland).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Exogenous free iodotyrosine inhibits iodide transport through the sequential intracellular events.

We describe a new function of exogenous iodotyrosine as a regulator of iodide transport. Porcine thyroid follicles in culture were preincubated with 0-20 mumol/l monoiodotyrosine or diiodotyrosine (DIT) in the presence of bovine thyrotropin (TSH) for 24 h; these iodotyrosines inhibited iodide uptake in a dose-response manner. Extracellular [125I]DIT was actively transported to the thyroid follicle in the presence of TSH or (Bu)2cAMP. Inhibition of iodide uptake by iodotyrosine required preincubation with iodotyrosine in the presence of TSH; without TSH, iodotyrosine was ineffective. Follicles preincubated with DIT for 24 h inhibited TSH-mediated cAMP production, which is an important signal for iodide transport. Inhibition of iodide uptake and cAMP generation by iodotyrosine was negated characteristically by 3-nitro-L-tyrosine, an inhibitor of iodotyrosine deiodinase, or by methimazole, an inhibitor of thyroid peroxidase. Our findings suggest that iodotyrosine regulates iodide transport through the following sequential intracellular events: TSH-dependent iodotyrosine transport into the thyroid cell; deiodination of iodotyrosine and release in iodide; iodine organification by the peroxidase system; inhibition of cAMP generation by organified iodine; and inhibition of iodide transport. Thus, exogenous iodotyrosine can serve as an inhibitor of thyroid hormone formation only when TSH is present.

Animals↗
PubMed1980

Chronic iodine toxicity in dairy cattle: blood chemistry, leukocytes, and milk iodide.

Preliminary data from farm herds fed excessive dietary iodide and displaying signs of iodism indicated hyperglycemia, hypocholesterolemia, and a neutrophilic-lymphopenic shift in blood leukocytes. Subsequently blood, milk, and urine were analyzed from 90 cows in 10 herds fed normal (average 16 mg/cow daily) or high (average 164 mg) iodide as ethylenediamine dihydriodide for prophylactic purposes and from one herd fed iodinated casein for 3 wk. Glucose, area nitrogen, and neutrophils were higher while cholesterol and lymphocytes were lower in blood from cows fed high iodide. Milk iodide averaged .37 +/- .03 ppm from normal and 2.16 +/- .25 from herds fed high iodide. Neutrophils, glucose, protein, and globulin of serum increased while lymphocytes, cholesterol, and thyroxine decreased as iodide in milk and urine increased. Signs of iodism included lacrimation, coryza, conjunctivitis, coughing, hair loss, and exophthalmus. These findings corroborate other reports that excessive iodide alters metabolism and is toxic to immune mechanisms, suggesting that dietary iodide should be limited to nutritional requirements and prolonged prophylactic or therapeutic use should be avoided.

Animals↗
PubMed1997

Protection of the maternal and fetal thyroid from radioactive contamination by the administration of stable iodide during pregnancy. An experimental evaluation in chimpanzees.

The safety and efficacy of the administration of stable iodide to protect the fetal thyroid from exposure to radioactive iodide were investigated in chimpanzees in weeks 19 to 21 of pregnancy. The mean 24-h uptake of iodide in the fetal thyroid, determined with 123I-, was 1.8%. Administration of stable potassium iodide (KI), 0.65, 1.95 or 6.5 mg per kg body weight, 1 h before tracer injection reduced the fetal uptake satisfactorily. Only the higher doses were effective after 20 h. Excess iodide may impair a child's thyroid status. However, adverse effects were not found during the 11 days the animals ingested these doses. Tracer concentrations in the amniotic fluid were 30- to 130-fold lower than in the urine. The dose to the fetus from radioactivity in the maternal bladder was estimated by computer simulation. The potential increment of the risk from this dose during the ingestion of stable iodide is smaller than the reduction of risk achieved by inhibiting the uptake of radioactive iodide by the fetal thyroid. The conclusion of the experiments is that stable iodide can be used safely and effectively to protect the fetal thyroid against contamination with radioactive iodine.

Animals↗
PubMed2000

Propidium iodide compares favorably with histology and triphenyl tetrazolium chloride in the assessment of experimentally-induced infarct size.

Quantitative assessment of infarct size after histology processing or by tetrazolium staining requires long reperfusion times to facilitate the delineation of the injured tissue. We evaluated the nucleic acid stain propidium iodide as an alternate technique for assessment of infarct size because it does not require extended reperfusion and is accomplished with more simple tissue processing. Eight mice underwent 45 min of coronary artery occlusion and 24 h of reperfusion, after which propidium iodide was administered and allowed to circulate for 15 min. Hearts were excised, sliced into transverse slices approximately 620 micro m thick, and photographed for determination of infarction with propidium iodide. Slices were processed by standard histology techniques, and infarction was evaluated using classical criteria of necrosis. In four other mice, infarct size was assessed by both triphenyl tetrazolium chloride and propidium iodide staining. A total of 46 slices were analysed and infarction was described as a percentage of the cross-sectional area of the slice. The correlation (r=0.94), orthogonal regression line (y=0.9x+1.8), and the percentage of the cross-section infarcted (histology 17.5+/-3.0%v propidium iodide 18.5+/-3.0%), demonstrates that infarct size assessment after propidium iodide staining or histology processing yields the same results. Similarly, propidium iodide measurement of infarct size was comparable to that obtained with TCC staining (22.5+/-4.1%v 25.4+/-5.4%, respectively, r=0.84). We conclude that propidium iodide staining yields accurate infarct size assessment and is a simpler alternative to tetrazolium staining or histologic processing.

Animals↗
PubMed1996

Separation of free iodide from other I-species in human serum - Quantification in serum pools and individual samples.

A method for the determination of free iodide in human serum has been developed. Iodide from pooled serum samples has been separated from the organic matter by SEC, subsequently freeze-dried and analyzed by ion chromatography. Investigations for recovery and precision have been carried out and provided sufficient results. For quality assurance ICP-MS has been taken additionally as a total I-detector. The iodide results of ICP-MS agree well with IC values. Iodine containing SEC- fractions from iodide-spiked samples has shown no increased I-values except that in the iodide fractions, proving that there has been no iodide conversion into other I-species (and vice versa) during the whole procedure. Free iodide from two serum pools of different healthy persons has been determined as 2.25 and 2.43 microg I(-)/l, respectively. The values are related to total iodine levels determined by ICP-MS. For comparative reasons a table of individual iodine and iodide values is presented.

Journal Article↗
PubMed1999

Discrimination of damaged/dead cells by propidium iodide uptake in immunofluorescently labeled populations analyzed by phase-sensitive flow cytometry.

We report a flow cytometric fluorescence lifetime-based method to discriminate damaged/dead from viable cells in immunofluorescently labeled populations using propidium iodide as a dye-exclusion viability probe. Fluorescence signals from propidium iodide and the anti-thymus cell-surface immunofluorescence marker fluorochromes, phycoerythrin and phycoerythrin/Texas Red (tandem conjugate), which have overlapping emission spectra with propidium iodide, are resolved based on differences in their fluorescence emission lifetimes using phase-sensitive detection. Mouse thymus cell samples were first labeled separately with anti-Thy 1.2 antibody directly conjugated to phycoerythrin and to phycoerythrin/Texas Red and propidium iodide. Labeled cells were then analyzed to determine the lifetimes of the immunofluorescence markers and propidium iodide. Based on these results, rat and mouse thymocytes labeled with anti-Thy 1.1 conjugated to phycoerythrin and anti-Thy 1.2 conjugated to phycoerythrin/Texas Red, respectively, were suspended in phosphate buffered saline containing propidium iodide, and were analyzed as they passed through a flow chamber and crossed a high-frequency, intensity-modulated (sinusoidal) laser excitation beam. The resulting immunofluorescence and propidium iodide signals were resolved based on differences in fluorescence lifetimes expressed as phase shifts using phase-sensitive detection and displayed as frequency distribution histograms and bivariate contour diagrams. This technology provides a new method to resolve immunofluorescence and propidium iodide signals from overlapping fluorescence emission spectra and a flow cytometric lifetime-based technique to quantify damaged/dead cells in immunofluorescence studies.

Animals↗
PubMed2004

[Enzymes involved in thyroid iodide organification].

Thyroid hormone biosynthesis depends on iodide uptake and its incorporation into the acceptor protein thyroglobulin (Tg), a high molecular weight protein secreted into the follicular lumen. The sodium-iodide symporter (NIS) is responsible for thyroid iodide uptake, the first step in thyroid hormonogenesis. Iodide is subsequently transported through the cellular membrane by pendrin (PDS) and then incorporated into Tg. Iodide oxidation and organification occur mainly in the thyrocyte apical surface and these reactions are catalyzed by thyroperoxidase (TPO) in the presence of hydrogen peroxide. Thus, thyroid iodide organification depends on TPO activity, which is modulated by the concentration of substrates (thyroglobulin and iodide) and cofactor (hydrogen peroxide). Hydrogen peroxide generation is catalyzed by the thyroid NADPH oxidase (ThOx), which is present in the apical pole of thyrocytes, is stimulated by thyrotropin and is inhibited by iodide. Hydrogen peroxide generation is the limiting step in thyroid hormone biosynthesis under iodine sufficiency conditions.

Hydrogen Peroxide↗
PubMed1987

Carbamazepine (Tegretol) inhibits in vivo iodide uptake and hormone synthesis in rat thyroid glands.

Decreased serum concentrations of T3 and T4 occur in patients treated with the anticonvulsant drug carbamazepine (CBZ), but with rare exception, these patients remain euthyroid. The mechanism that accounts for diminished hormone levels is unknown, and our objective was to study the direct effect of CBZ on iodide uptake and hormone synthesis in thyroid glands of CBZ-treated and pair-fed control rats. Chronic ingestion (per os) of CBZ in male rats reduced the four hour thyroid 131I-iodide uptake by approximately 60%. This inhibition occurred after the animals had received sufficient CBZ to attain plasma CBZ concentrations of 0.8 microgram/ml. Continued treatment with CBZ ranging from 560 to 800 mg/kg/day for 14 days did not result in further inhibition of iodide uptake even though the plasma CBZ concentrations had increased 6-20 fold. No inhibition of iodide uptake was apparent when the animals initially received CBZ ranging from 40 to 152 mg/kg body weight for 22 days when there were no detectable levels of plasma CBZ. Overall growth rates of CBZ-treated rats were slightly (6-10%) less than the pair-fed control animals. Plasma T4 concentrations were reduced by 18% (p less than 0.05) in the CBZ-fed animals, while T3 concentrations were diminished by 53% (p less than 0.01). CBZ appeared to alter thyroidal iodide transport because the thyroid:plasma iodide ratios were decreased by 26% in the drug-treated rats. The distribution of radioiodine in thyroidal iodoamino acids was essentially the same in both groups of rats but the absolute quantities of radioiodine were more than 2.5 times greater in the control rats. CBZ failed to inhibit peroxidase-catalyzed iodide and guaiacol oxidation in vitro. No differences in thyroid gland morphology were noted in the two groups of animals, but weights of the glands from the CBZ-fed animals increased by 25% after 42 days. It is concluded that CBZ, or its metabolites, has a direct inhibitory effect on iodide utilization and hormone synthesis by the thyroid gland.

Animals↗
PubMed2000

Permeability of boar and bull spermatozoa to the nucleic acid stains propidium iodide or Hoechst 33258, or to eosin: accuracy in the assessment of cell viability.

This study was designed to assess whether nucleic acid stains such as propidium iodide and Hoechst 33258 and the cytosolic stain eosin identified equivalent proportions of non-viable cells. Sub-samples of boar spermatozoa stored for up to 72 h, and frozen bull spermatozoa stored in straws and thawed before staining, were exposed to either propidium iodide or Hoechst 33258 alone or in combination. Additional sub-samples were stained with eosin-nigrosin and subsequently with Giemsa. The proportion of non-viable cells identified by propidium iodide alone was equivalent to that observed when it was used in combination with the other fluorescent probe. Similar results were observed for Hoechst 33258. However, direct microscopic examination of sub-samples exposed to both stains revealed that a proportion of spermatozoa stained with propidium iodide did not incorporate Hoechst 33258. This was found consistently in boar and bull spermatozoa under the different experimental conditions used. Quantification showed that the proportion of propidium iodide-positive cells was significantly higher than Hoechst 33258-positive cells. Furthermore, the proportion of propidium iodide-positive cells was higher than cells stained with eosin, but no differences were found between the number of cells stained with Hoechst 33258 or eosin. The proportion of cells stained with propidium iodide was positively correlated with the proportion stained with either Hoechst 33258 or eosin, despite the observation that more cells incorporated propidium iodide. Taken together, these results indicate that there are differences in the ability of fluorescent probes to identify non-viable sperm cells and that this should be considered when staining protocols are used to analyse sperm viability, or when viability is used as a discriminating factor in functional studies, such as those related to acrosomal exocytosis.

Analysis of Variance↗
PubMed1999

Follicular thyroglobulin suppresses iodide uptake by suppressing expression of the sodium/iodide symporter gene.

A major function of the thyrocyte is to take up and concentrate iodide. This is needed for thyroid hormone synthesis and is accomplished by the sodium iodide symporter (NIS), whose expression and activity are up-regulated by TSH. Recently, we reported that follicular thyroglobulin (TG) is a potent suppressor ofthyroid-specific gene expression and can overcome TSH-increased gene expression. We suggested this might be a negative feedback, autoregulatory mechanism that counterbalanced TSH stimulation of follicular function. In this report, we support this hypothesis by coordinately evaluating TG regulation of NIS gene expression and iodide transport. We show that physiological concentrations of TG similarly and significantly suppress TSH-increased NIS promoter activity, NIS protein, and NIS-dependent iodide uptake as well as RNA levels. We show, in vivo, that TG accumulation at the apical membrane of a thyrocyte facing the follicular lumen is associated with decreased uptake ofradioiodide. It is likely, therefore, that TG suppresses NIS-dependent iodide uptake and NIS gene expression in vivo, as is the case in vitro. RNA levels of NIS and vascular endothelial growth factor/vascular permeability factor, which has been reported to be TSH regulated and possibly associated with TSH-increased iodide uptake, are coordinately decreased by follicular TG as a function of concentration and time. Also, removal of follicular TG from the medium, but not TSH, coordinately returns NIS and vascular endothelial growth factor/vascular permeability factor RNA levels to their TSH-stimulated state. TG accumulated in the follicular lumen appears, therefore, to be a negative feedback regulator of critical TSH-increased follicular functions, iodide uptake, and vascular permeability.

Animals↗
PubMed1999

Prostate-specific antigen (PSA) promoter-driven androgen-inducible expression of sodium iodide symporter in prostate cancer cell lines.

Currently, no curative therapy for metastatic prostate cancer exists. Causing prostate cancer cells to express functionally active sodium iodide symporter (NIS) would enable those cells to concentrate iodide from plasma and might offer the ability to treat prostate cancer with radioiodine. Therefore, the aim of our study was to achieve tissue-specific expression of full-length human NIS (hNIS) cDNA in the androgen-sensitive human prostatic adenocarcinoma cell line LNCaP and in subcell lines C4, C4-2, and C4-2b in vitro. For this purpose, an expression vector was generated in which full-length hNIS cDNA coupled to the prostate-specific antigen (PSA) promoter has been ligated into the pEGFP-1 vector (NIS/PSA-pEGFP-1). The PSA promoter is responsible for androgen-dependent expression of PSA in benign and malignant prostate cells and was therefore used to mediate androgen-dependent prostate-specific expression of NIS. In addition, two control vectors were designed, which consist of the pEGFP-1 vector containing the PSA promoter without NIS cDNA (PSA-pEGFP-1) and NIS cDNA without the PSA promoter (NIS-pEGFP-1). Prostate cancer cells were transiently transfected with each of the above-described expression vectors, incubated with or without androgen (mibolerone) for 48 h, and monitored for iodide uptake activity. In addition, stably transfected LNCaP cell lines were established for each vector. Prostate cells transfected with NIS/PSA-pEGFP-1 showed perchlorate-sensitive, androgen-dependent iodide uptake in a range comparable to that observed in control cell lines transfected with hNIS cDNA. Perchlorate-sensitive iodide uptake was not observed in cells transfected with NIS/PSA-pEGFP-1 and treated without androgen or in cells transfected with the control vectors. In addition, prostate cancer cell lines without PSA expression (PC-3 and DU-145) did not show iodide uptake activity when transfected with NIS/PSA-pEGFP-1. Western blotting of LNCaP and C4-2b cell membranes transfected with NIS/PSA-pEGFP-1 using a monoclonal antibody that recognizes the COOH-terminus of hNIS revealed a band with a molecular weight of 90,000 that was not detected in androgen-deprived cells or in cells transfected with the control vectors, as well as a minor band at Mr 150,000 in transiently transfected LNCaP cell membranes. In conclusion, tissue-specific androgen-dependent iodide uptake activity has been induced in prostate cancer cells by PSA promoter-directed NIS expression. This study represents an initial step toward therapy of prostate cancer with radioiodine.

Adenocarcinoma↗
PubMed2003

Probasin promoter (ARR(2)PB)-driven, prostate-specific expression of the human sodium iodide symporter (h-NIS) for targeted radioiodine therapy of prostate cancer.

Prostate cancer is one of the most promising candidates for sodium iodide symporter (NIS)-mediated gene therapy. Adenovirus-mediated expression of NIS that is driven by prostate-specific promoters induces generous radioiodine accumulation in prostate cancer cells that may be used for therapy with (131)I. We have recently developed a replication-deficient adenovirus carrying the human NIS cDNA linked to a composite probasin promoter, ARR(2)PB, aiming toward specific expression of the human NIS gene (h-NIS) in prostate tissue for targeted radioactive iodide therapy of prostate cancer (Ad-ARR(2)PB/hNIS). The ability of Ad-ARR(2)PB/hNIS to cause NIS expression in tumor cells was characterized by iodide uptake assay and compared with Ad-CMV/hNIS in which the h-NIS expression is driven by the cytomegalovirus (CMV) promoter. Androgen-dependent prostate cancer cell lines (LNCaP) and non-prostate origin tumor cell lines (SNU449, MCF-7, HCT116, OVCAR-3, and Panc-1) were infected with the viral constructs, and perchlorate-sensitive (125)I uptake and NIS protein expression were measured. Ad-ARR(2)PB/hNIS-infected LNCaP cells showed androgen-dependent and perchlorate-sensitive iodide uptake. Iodide accumulation in LNCaP cells infected with Ad-ARR(2)PB/hNIS, followed by incubation with synthetic androgen, was 5.3-fold increased compared with those coincubated with perchlorate (15,184 +/- 1,173 cpm versus 2,837 +/- 187 cpm). Ad-ARR(2)PB/hNIS-infected LNCaP cells revealed a 3.2-fold increase of iodide accumulation compared with those infected with Ad-CMV/hNIS (multiplicity of infection = 30). Iodide uptake in a panel of non-prostate tumor cell lines infected with Ad-ARR(2)PB/hNIS was no more than 2,500 cpm, demonstrating the tissue specificity of this construct. These results indicate that Ad-ARR(2)PB/hNIS can be used to achieve high-magnitude and tissue-specific expression of h-NIS in prostate tissue and is a promising candidate for cancer gene therapy of prostate cancer.

Adenoviruses, Human↗
PubMed2003

Capillary zone electrophoretic determination of iodide in seawater using transient isotachophoresis with artificial seawater as the background electrolyte.

We describe an application of capillary zone electrophoresis (CZE) with transient isotachophoresis (ITP) as the on-line concentration procedure for the determination of iodide in seawater. The effective mobility of iodide was decreased by the addition of 10 mM cetyltrimethylammonium chloride (CTAC) to an artificial seawater background electrolyte (BGE) so that transient ITP functioned and iodide was separated from other coexisting anions such as bromide, nitrite, and nitrate in seawater samples. After sample injection, 600 mM acetate was separately injected into the capillary as the terminating ion to generate transient ITP. The limit of detection (LOD) for iodide was 3.0 microg/L. The LOD was obtained at a signal-to-noise ratio (S/N) of 3. The values of the relative standard deviation (RSD) of peak area, peak height, and migration time for iodide were 2.9, 2.1, and 0.6%. The proposed method was applied to the determination of iodide in seawater collected around the Osaka Bay. The results obtained by use of the calibration graph were agreed with those obtained by the addition of the standard solutions for iodide.

Calibration↗