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PubMed1996

Distribution, biomagnification, and elimination of butyltin compound residues in common cormorants (Phalacrocorax carbo) from Lake Biwa, Japan.

Concentrations of butyltin compounds (BTs) were determined in various body tissues of common cormorants (Phalacrocorax carbo) collected from the Lake Biwa, Japan. Elevated concentrations of butyltins were detected in the feathers of cormorants. Among other organs and tissues, butyltin levels were also higher in the kidney (290+/-150 ng/g) and liver (270+/-260 ng/g), ranging from 115 to 544 ng/g and 142 to 1007 ng/g (wet wt basis), respectively. The accumulation of BTs in cormorant bodies was in the order of MBT>DBT>TBT and their organ specific burdens were in the order of muscle>/=feathers>skin>liver>rest of the tissues and organs. The higher levels of BTs residues in feather suggested the excretion of about one fourth of their body burden during a complete molting cycle, which has been a natural detoxification mechanism in these birds. Based on the whole body concentrations of BTs in cormorants (42-160 ng/g wet wt) and fish (10-55 ng/g wet wt) biomagnification factors were assessed to be in the range of 1.1-4.1. To our knowledge, this is the first fundamental study to substantially indicate the contamination and kinetics of BTs in wild birds.

Animals↗
PubMed1979

The behavioral and neuropathologic sequelae of intoxication by trimethyltin compounds in the rat.

Trimethyltin, when given by gavage to rats, has an LD50 of 12.6 mg/kg. Signs of poisoning include tremors, hyperexcitability, aggressive behavior, weight loss, and convulsions. After single (10 mg/kg) or repeated weekly doses (a maximum of four) of 4 mg/kg, rats, up to a survival time of 70 days, were perfusion-fixed for light microscopy. Trimethyltin was assayed in brain and blood in rats after similar treatments. Trimethyltin is cumulative and persistent and binds with high affinity to hemoglobin. Trimethyltin, unlike triethyltin, does not produce white matter edema in rats but does cause bilateral and symmetrical neuronal alterations involving the hippocampus (largely sparing the Sommer sector), pyriform cortex, amygdaloid nucleus, and neocortex. The earliest alteration was loss or dispersal of Nissl substance, then clumping of nuclear chromatin, followed by shrinkage and fragmentation of the nucleus within shrunken eosinophilic cytoplasm. These changes were associated with approximately 1.4 microgram trimethyltin/g wet weight in brain tissue 1 day after the second dose of 4 mg/kg or 2 days after a single dose of 10 mg/kg. Signs of poisoning gradually disappeared, and 4 rats surviving 70 days appeared normal, although their brains had severe damage with cell loss in the hippocampi and each pyriform cortex. Treatment of rats with trimethyltin, therefore, provides a chronic preparation with consistent lesions in the hippocampus of use in other behavioral and neuroanatomic studies. (Am J Pathol 97:59--82, 1979).

Animals↗
PubMed1991

Bis(tri-n-butyltin)oxide induces programmed cell death (apoptosis) in immature rat thymocytes.

In order to characterise the mechanism of cytotoxicity of the immunotoxic organotin compound bis(tri-n-butyltin)oxide (TBTO) to lymphoid cells, isolated thymocytes from immature rats were exposed to TBTO (0.1-5 microM) for up to 6 h. At lower TBTO concentrations (0.1 and 1 microM) vital staining showed that only marginal loss of viability occurred, although morphological studies demonstrated increased numbers of cells with abnormal features indicative of programmed cell death (apoptosis). These changes included nuclear chromatin condensation (which was associated with increased DNA fragmentation), cytoplasmic contraction and formation of membrane bound apoptotic bodies. When visualised by agarose gel electrophoresis, genomic DNA appeared as a series of fragments with a repeat multiple of 180-200 base pairs. Comparable morphological changes and cleavage of DNA into oligonucleosomal fragments were evident in thymocytes incubated with 10 microM methyl prednisolone hemisuccinate (MPS); a glucocorticoid hormone known to induce programmed cell death in thymocytes. Marked cytotoxicity associated with degenerative changes indicative of necrosis was observed in thymocytes incubated with 5 microM TBTO. These findings indicate that, at levels which are not overtly cytotoxic, TBTO is capable of inducing programmed cell death in rat thymocytes. This suggests a possible mechanism for the T-cell immunodeficiency previously reported for TBTO in vivo.

Animals↗
PubMed2000

Evaluation of environmental levels and biological impact of TBT in Malta (central Mediterranean).

Chemical monitoring for butyltins in bulk seawater, surface microlayer and superficial sediments determined that the two main local sources of marine contamination by tributyltin (TBT) compounds in Malta are ship-repairing dockyards and marinas. In bulk seawater, TBT values ranged from below the detection limit of 5 ng Sn l(-1) to 300 ng Sn l(-1); in sediments derived from the most polluted areas, TBT concentrations as high as 1500 ng Sn g(-1) were measured. At TBT levels found in local harbours, several sublethal biological responses are possible and were observed, including a significant reduction in MFO enzyme system activities of fish; digestive cell atrophy in the oyster Ostrea edulis; and induction of imposex in the snail Hexaplex trunculus. The latter two responses are evident at TBT concentrations below the environmental quality standard (20 ng TBT l(-1)). The ecological implications of these results are discussed and it is concluded that exposure of marine organisms to TBT in local harbours may be expected to lead to a reduction in the long-term survival of a number of such organisms. For these reasons, both the use of TBT-based antifouling paints for pleasure boats as well as drydock practices need to be controlled by appropriate regulations and their enforcement.

Animals↗
PubMed2001

Impaired growth in the polychaete Armandia brevis exposed to tributyltin in sediment.

Juveniles of the opheliid polychaete, Armandia brevis, were exposed to sediment-associated tributyltin (TBT) for 42 days to evaluate toxicity and bioaccumulation. Growth in this species was inhibited in a dose-response fashion by increasing concentrations of TBT. Even though the biota-sediment accumulation factor (BSAF) for TBT declined for the higher sediment concentrations, the total butyltins in tissue increased over all sediment concentrations. At the highest sediment concentrations, polychaetes bioaccumulated less TBT than expected, which was most likely due to reduced uptake and continued metabolism of the parent compound. The less than expected BSAF values exhibited by animals at the exposure concentrations causing severe effects are an important finding for assessing responses in the field. It appears that severe biological effects can occur in long-term experiments without the expected high tissue concentrations; an observation likely explained by altered toxicokinetics. Analysis of variance determined the lowest observed effect concentration for growth to be 191 ng/g sediment dry wt. for 21 days of exposure and 101 ng/g sediment dry wt. at day 42, indicating that 21 days was insufficient for delineating the steady-state toxicity response. When based on regression analysis, the sediment concentration causing a 25% inhibition in growth at 42 days exposure was 93 ng/g dry wt. (total organic carbon = 0.58%). A dose-response association was also determined for polychaete net weight and TBT in tissue. The tissue residue associated with a 25% reduction in growth was 2834 ng/g dry wt. at day 42. A comparison of these results with previous work indicates that juveniles are approximately three times more sensitive than adults to TBT exposure. The sediment concentrations affecting growth in this species are commonly found in urban waterways indicating potentially severe impacts for this and other sensitive species.

Animals↗
PubMed2003

Inhibition of rat testis microsomal 3beta-hydroxysteroid dehydrogenase activity by tributyltin.

In this study, we have examined the effects of a range of organotin compounds (mono-, di-, tributyltin, mono-, di-, trioctyltin) on the activities of rat testis microsomal 3beta-hydroxysteroid dehydrogenase (3beta-HSD), 17-hydroxylase (17-OHase) and 17beta-hydroxysteroid dehydrogenase (17beta-HSD). 17-OHase activity was inhibited by more than 50% compared with the control rate by 59 microM tributyltin (TBT) but other organotin compounds showed no inhibition. 17beta-HSD activity was unaffected by all organotins tested. 3beta-HSD was inhibited by monooctyltin (81 microM) and by TBT at all concentrations tested in a dose-dependent manner, with almost complete loss of activity at TBT concentrations of 12 microM. The mechanism of inhibition of 3beta-HSD was investigated in kinetic analysis with 0-12 microM TBT. Three rat testis microsomal preparations were incubated with dehydroepiandrosterone as the steroid substrate ranging from 1 to 10,000 nM. Tributyltin was primarily a competitive inhibitor of 3beta-HSD activity, causing an increase in the value of the K(m(app)). However, the mechanism was not entirely competitive as while there was an increase in K(m(app)), a decrease in the V(max(app)) was also observed with increasing concentrations of TBT. Slope and intercept replots demonstrated that the K(i)((app)) from slope replots was around 2.7 microM whereas the K(i)((app)) value from intercept replots was around 30 microM. When compared with the K(m(app)) for 3beta-HSD of around 0.42 microM, TBT could be an effective inhibitor of this enzyme.

17-Hydroxysteroid Dehydrogenases↗
PubMed2004

Toxicity of tributyltin to willow trees.

BACKGROUND: Tributyltin is an organotin compound, used as an antifouling agent in ship paint, with heavy impact on the marine environment. Contaminated dredged harbor sludge is now dumped on land. The toxicity of tributyltin (TBT) to trees has not yet been quantified. Eventually, a vegetation cover on the dumped sludge could be established for the purpose of non-food cash crop production and phytoremediation. METHODS: The phytotoxicity of tributyltin chloride (TBTCl) and tributyltin hydride (TBTH) was measured at pH 4 and at pH 7 using the willow tree transpiration test. Different pH levels of the nutrient solutions were achieved by adding ammonium salt (low pH) or nitrate (high pH) as nitrogen source. RESULTS AND DISCUSSION: At low pH (pH 4), all trees showed symptoms of poor health. Transpiration decreased at concentrations above or equal to 0.1 mg TBTCl/l and 1 mg TBTH/L. The TBT toxicity was more pronounced at pH 7. The trees survived even the highest dose of 10 mg/l TBTCl or TBTH, although their growth and transpiration was strongly reduced. CONCLUSION: In contrast to other organisms, TBTCl and TBTH were less toxic to higher plants. RECOMMENDATIONS AND OUTLOOK: The toxicity of TBT is no hindrance for establishing vegetation on TBT-contaminated sludge. Phytoremediation and cash crop production could be possible with suitable plants.

Environmental Pollutants↗
PubMed1984

Effect of triethyltin on autonomic and behavioral thermoregulation of mice.

The organotin compound, triethyltin (TET), produces toxic effects in a variety of physiological systems. Thermoregulatory control appears to be especially susceptible to TET toxicity, since TET administration has been shown to cause a pronounced hypothermia in rats. To further elucidate effects of TET on thermoregulation, we measured metabolic rate, evaporative water loss (EWL), body temperature, and preferred ambient temperature (Ta) of mice treated intraperitoneally with TET (bromide salt). At a Ta of 23 to 24 degrees C, TET (6 and 8 mg/kg) inhibited metabolic rate by 23 and 66%, respectively. TET resulted in hypothermia at Ta's of 20 and 30 degrees C but not 35 degrees C. TET had little effect on EWL. Mice given TET at doses of 4, 6, and 8 mg/kg selected a cooler Ta (ca. 25 degrees C) compared to controls (ca. 29 degrees C). Thus, the mice selected a Ta associated with a hypothermic body temperature. At a relatively cool Ta, mice treated with TET had a reduced rate of heat production and, consequently, were hypothermic. At a relatively warm Ta, TET had no effect on heat production and did not increase active heat dissipation (i.e., EWL), thus the mice remained normothermic. The behavioral data indicate that TET evokes a type of regulated hypothermia in mice.

Animals↗
PubMed2006

Estrogens counteract the masculinizing effect of tributyltin in zebrafish.

Recently, it has been demonstrated that the biocide tributyltin (TBT) can interfere with fish sex differentiation, leading to a bias of sex toward males. On the contrary, it is well known that estrogenic compounds can induce fish feminization. Yet, the combined effects of mixtures of androgenic and estrogenic compounds on fish sex differentiation have never been investigated before, even though in the environment animals are frequently exposed to both groups of xenobiotics. Therefore, in order to investigate whether exposure to estrogenic compounds can block the masculinizing effect of TBT, 5 days post-fertilization zebrafish (Danio rerio) larvae were exposed for a four month period to TBT and to the synthetic estrogen-ethinylestradiol (EE2). The fish were fed a diet containing TBT at nominal concentrations of 25 and 100 ng TBT/g, and two groups of animals were also dosed with TBT plus EE2 at nominal water concentration of 3.5 ng/L, using a flow-through design. As expected, fish exposed to TBT showed a bias of sex toward males (62.5% males in control tanks and 86% and 82% in TBT 25 and TBT 100 ng TBT/g, respectively). Co-exposure to EE2 completely blocked the masculinizing effect of TBT, with 7% males in the TBT 25 ng/g + EE2 treatment and 0% in the EE2 alone and in the TBT 100 ng/ + EE2 exposed groups. These results clearly indicate that EE2, at environmentally relevant concentrations, can block the TBT masculinizing effects in zebrafish, which suggests that in the aquatic environment the presence of estrogens may neutralize the fish masculinizing effect of TBT. Our findings highlight the need of testing the combined effects of contaminants, as single exposure studies may not be sufficient to predict the effects of mixtures of xenobiotics with antagonistic properties.

Animals↗
PubMed1991

Triorganotins inhibit the mitochondrial inner membrane anion channel.

The inner membrane of liver and heart mitochondria possesses an anion uniport pathway, known as the inner membrane anion channel (IMAC). IMAC is inhibited by matrix Mg2+, matrix H+, N,N'-dicyclohexycarbodiimide, mercurials and amphiphilic amines such as propranolol. Most of these agents react with a number of different mitochondrial proteins and, therefore, more selective inhibitors have been sought. In this paper, we report the discovery of a new class of inhibitors, triorganotin compounds, which block IMAC completely. One of the most potent, tributyltin (TBT) inhibits malonate uniport via IMAC 95% at 0.9 nmol/mg. The only other mitochondrial protein reported to react with triorganotins, the F1F0ATPase, is inhibited by about 0.75 nmol/mg. The potency of inhibition of IMAC increases with hydrophobicity in the sequence trimethyltin much less than triethyltin much less than tripropyltin less than triphenyltin less than tributyltin; which suggests that the binding site is accessible from the lipid bilayer. It has long been established that triorganotins are anionophores able to catalyze Cl-/OH- exchange; however, TBT is able to inhibit Cl- and NO3- transport via IMAC at doses below those required to catalyze rapid rates of Cl-/OH- exchange. Consistent with previous reports, the data indicate that about 0.8 nmol of TBT per mg of mitochondrial protein is tightly bound and not available to mediate Cl-/OH- exchange. We have also shown that the mercurials, p-chloromercuribenzene sulfonate and mersalyl, which only partially inhibit Cl- and NO3- transport can increase the IC50 for TBT 10-fold. This effect appears to result from a reaction at a previously unidentified mercurial reactive site. The inhibitory dose is also increased by raising the pH and inhibition by TBT can be reversed by S2- and dithiols but not by monothiols.

4-Chloromercuribenzenesulfonate↗
PubMed2003

Effect of tributyltin on trout blood cells: changes in mitochondrial morphology and functionality.

The aquatic environment is the largest sink for the highly toxic organotin compounds, particularly as one of the main sources is the direct release of organotins from marine antifouling paints. The aim of this study was to investigate the mitochondrial toxicity and proapoptotic activity of tributyltin chloride (TBTC) in teleost leukocytes and nucleated erythrocytes, by means of electron microscopy investigation and mitochondrial membrane potential evaluation, in order to provide an early indicator of aquatic environmental pollution. Erythrocytes and leukocytes were obtained from an inbred strain of rainbow trout (Oncorhynchus mykiss). Transmission electronic micrographs of trout red blood cells (RBC) incubated in the presence of TBTC at 1 and 5 microM for 60 min showed remarkable mitochondrial morphological changes. TBTC-mediated toxicity involved alteration of the cristae ultrastructure and mitochondrial swelling, in a dose-dependent manner. Both erythrocytes and leukocytes displayed a consistent drop in mitochondrial membrane potential following TBTC exposure at concentrations >1 microM. The proapoptotic effect of TBTC on fish blood cells, and involvement of mitochondrial pathways was also investigated by verifying the release of cytochrome c, activation of caspase-3 and the presence of "DNA laddering". Although mitochondrial activity was much more strongly affected in erythrocytes, leukocytes incubated in the presence of TBTC showed the characteristic features of apoptosis after only 1 h of incubation. Longer exposures, up to 12 h, were required to trigger an apoptotic response in erythrocytes.

Animals↗
PubMed1983

Nucleotide and bivalent cation specificity of the insulin-granule proton translocase.

1. The nucleotide and bivalent cation specificity of the proton translocase activity of insulin secretory granules was investigated by assessing the inhibitor-sensitive rates of nucleotide hydrolysis by these organelles in relation to their chemiosmotic properties. 2. The relative rates of nucleotide hydrolysis by freeze/thawed granule preparations were: Mg2+ATP (100%) greater than Mg2+GTP (55%) greater than Mg2+UTP (48%) greater than Mg2+ITP (44%) greater than Mg2+CTP (23%) greater than Mg2+TTP (20%), and by intact granules were: Mg2+ATP (100%) greater than Mg2+ITP (74%) greater than Mg2+GTP (60%) greater than Mg2+CTP (35%). Mg2+ATP, Mg2+GTP and Mg2+ITP hydrolyses were inhibited by tributyltin and stimulated, in intact granules, by the protonophore carbonyl cyanide p-trifluoromethoxyphenylhydrazone; Mg2+CTP hydrolysis was not markedly affected by these compounds. Correspondingly, only Mg2+ATP, Mg2+GTP and Mg2+ITP produced large changes in the delta psi and delta mu H+ across the granule membrane. 3. The relative rates of maximal ATPase activity stimulated by bivalent cations in freeze/thawed granule preparations were: Mg2+ (100%) greater than Mn2+ (82%) greater than Ca2+ (40%) greater than Co2+ (36%) greater than Zn2+ (0%), and in intact granules were: Mg2+ (100%) greater than Mn2+ (85%) greater than Co2+ (61%) greater than Ca2+ (42%). Tributyltin and carbonyl cyanide p-trifluoromethoxyphenylhydrazone affected Mg2+-, Mn2+- and Co2+-activated, but not Ca2+-activated, ATP hydrolysis. Correspondingly, only Mg2+, Mn2+ and Co2+ supported the generation of a delta psi and delta mu H+ across granule membranes in the presence of ATP. 4. The results were consistent with a single proton translocase that had its catalytic site exposed on the external face of the granule membrane. The indicated specificity (Mg2+ATP = Mn2+ATP greater than Co2+ATP greater than Mg2+GTP greater than Mg2+ITP) was similar to that of enzymes described in membrane fractions prepared from adenohypophyseal tissue, adrenal chromaffin granules and yeast vacuoles. The insulin-granule activity thus appears to be a type of proton translocase, which is characteristic of intracellular storage vesicles in eukaryotic cells.

Adenosine Triphosphatases↗
PubMed1990

Effects of ozone, hexachlorobenzene, and bis(tri-n-butyltin)oxide on natural killer activity in the rat lung.

The respiratory tract is a major route of exposure to noxious agents as well as pathogens such as viruses. Natural killer (NK) activity is an important first line of defense to virally infected cells as well as certain neoplasms; therefore, testing the effects of exposure to toxic compounds on this activity is important in understanding the immunotoxic potential of the compound. Lymphoid cell suspensions, obtained after enzymatic dispersion of rat lungs and purification over nylon wool columns, showed in vitro natural killer activity toward YAC lymphoma cells. Validation of the test with well-known NK activity stimulators such as Bacillus Calmette-Guérin (BCG), interleukin-2 (IL-2), interferon (IFN), and inhibitors like anti-asialo-GM1 (ganglio-n-tetrasylceramide) antibody confirmed the reliability of the test as an assay for detecting NK activity in rat lungs. Using this assay, we studied the effects of exposure to ozone (O3), hexachlorobenzene (HCB), and bis(tri-n-butyltin)oxide (TBTO) on NK activity in rat lung. Inhalation exposure to O3 for 7 days at 0.4 and 0.8 mg/m3 resulted in stimulation, and exposure at 1.6 mg O3/m3 resulted in suppression of NK activity. Oral exposure to HCB in concentrations of 150 and 450 mg/kg food for 6 weeks suppressed NK activity in rat lungs in a dose-related manner. This was also true for 6 weeks of oral exposure of rats to 20 and 80 mg TBTO/kg food, but to a lesser extent. In summary, we have developed and validated a method to measure the effects of (toxic) substances on NK activity in rat lung.

Animals↗
PubMed2001

Effect of solid surface composition on the migration of tributyltin in groundwater.

Tributyltin (TBT) is the most important organotin compound that has been introduced into aquatic ecosystems. A better understanding of its interactions with solid surfaces is essential to estimate the possibilities of TBT migration through subsurface environments. For this purpose, TBT sorption onto a porous matrix of natural origin, a quartz sand as an aquifer material, was studied at low concentration levels with a monodirectional model of column type allowing sequential investigation of sorption and desorption processes. Different treatments of the solid phase were performed by injecting alkaline solutions, NaOH at pH 10.8 or NaClO-NaCl at pH 11.5, by decreasing the ionic strength or by adding kaolinite to change the surface composition and properties. The removal of iron and aluminum (hydr)oxides from the sand surface did not affect so much the sorption (decrease in 14% as compared to sorption on the raw sand). The original use of X-ray photoelectron spectroscopy to control treatment efficiency and to characterize sand surface modifications permitted to relate TBT sorption onto the aquifer material to quartz, the main component of the sand, and clay minerals (mainly kaolinite) present at trace levels at the sand surface. A first attempt of transport modeling with these two surface sites showed the consistency of our assumption. Moreover, estimation of Langmuir-type constants showed that TBT sorption affinity for the quartz surface (KL = 26.7 L micromol(-1)) was much greater than for kaolinite (KL = 6.3 L micromol(-1)).

Adsorption↗
PubMed2002

Expression of CD16, CD18 and CD56 in tributyltin-exposed human natural killer cells.

Tributyltin (TBT) was produced in large quantities for use in wood preservation, marine antifouling paints, disinfection of circulating industrial cooling waters and slime control in paper mills. TBT is found in dairy products, meat and fish. We and others have shown that there are measurable levels of TBT in human blood. BTs appear to increase the risk of cancer and viral infections in exposed individuals. In previous studies, we demonstrated that the NK-cytotoxic function of lymphocytes was greatly diminished after a 1-h exposure to 300 nM TBT or a 24-h exposure to 200 nM TBT. Inhibition induced by a 1-h exposure to 300 nM TBT continues even after removal of the compound. There is also decreased ability of NK cells to bind to tumor target cells when they have been exposed to 200 nM TBT for 24 h. This loss of binding function is not seen when NK cells are exposed to 300 nM TBT for 1 h. However, NK cells exposed to 300 nM TBT for 1 h and then incubated in TBT-free media for 24, 48 or 96 h, show a significant loss of tumor-binding function by 96 h. The effects of TBT on cell surface molecules that are crucial to NK cell function is investigated. The data indicate there is a loss of expression of CD16 and CD56 on NK cells exposed to 200 nM TBT for 24 h. There is no decrease in expression of any of the markers studied when NK cells are exposed to 300 nM TBT for 1 h, consistent with the fact that a 1-h exposure has no effect on the ability of NK cells to bind to tumor targets. However, when NK cells are exposed to 300 nM TBT followed by 24, 48 or 96 h incubations in TBT-free media, there is a significant loss of CD16 and CD18 expression after 24 h and of CD16 and CD56 expression after 48 and 96 h.

Adolescent↗
PubMed2003

Sex alteration in soft-shell clams (Mya arenaria) in an intertidal zone of the Saint Lawrence river (Quebec, Canada).

The purpose of this study was to verify whether any changes in sex ratio might occur in soft-shell clams (Mya arenaria) located in an intertidal harbor zone located at the mouth of the Saguenay Fjord in the Saint Lawrence estuary (Baie Sainte-Catherine (BSC), Québec, Canada) likely to be contaminated by organotin compounds. Bivalves were harvested at the BSC harbor site and from two reference sites. Condition index (weight to length ratio), gonado-somatic index, sex ratio, vitellin-like proteins, organotin concentrations in gonad tissue, maturation stages of the gonads, the number of estradiol-17beta binding sites and the capacity of female gonad extracts to produce estradiol-17beta were determined in collected animals. Results showed that sex ratio in clams was significantly skewed toward males. Moreover, the condition and gonad-somatic indices, vitellin-like proteins in female gonads and the capacity of female gonads to produce estradiol-17beta were significantly reduced at the harbor site with respect to the reference sites. Maturation status of male gonads was clearly delayed at the harbor site. Additionally, gonad tissue contained tributyltin (TBT) at an average level of 109+/-18 ngSn/gdry wt. at the harbor site while organotins were not detected from the reference sites. Finally, female gonads had a higher number of unoccupied estradiol binding sites at the harbor site indicating low levels of this steroid in this tissue. Overall, this paper is first to report that clams collected in the vicinity of a TBT contaminated harbor are subject to masculinizing effects which seems to be consistent with biological effects that organotins are known to exert toward some other marine invertebrates.

Animals↗
PubMed2006

Effects of tributyltin on the development of atopic dermatitis-like eruptions in DS-Nh mice.

BACKGROUND: In the last few decades, numerous chemical compounds have been produced as a result of industrial development. At the same time, the number of atopic dermatitis (AD) patients has been increasing. It has been reported that tributyltin (TBT) compounds have effects not only on the reproductive system but also on the immune system. OBJECTIVE: To investigate whether TBT has an effect on AD, we fed a diet containing TBT to DS-Nh mice, which spontaneously developed dermatitis under conventional conditions. METHODS: DS-Nh mice fed TBT or a control diet were examined for skin changes, number of Staphylococcus aureus on the skin and serum IgE levels. To determine Th1/Th2 cytokine production by lymphocytes, lymphocytes of DS-Nh mice fed TBT and of controls were cultured with staphylococcal enterotoxin B and cytokine levels in the supernatants were measured by ELISA. We observed not only spontaneous dermatitis but also dermatitis induced by sensitization with 2,4,6-trinitrochlorobenzene (TNCB). RESULTS AND CONCLUSION: The AD-like lesions induced by TNCB sensitization were more severe in the mice fed TBT than in those fed the control diet. A greater increase in S. aureus on the skin was observed in the mice fed TBT than in the mice fed the control diet. A decrease in IFN-gamma production and an increase in IL-5 and IL-13 production were observed in the mice fed the TBT diet and treated with TNCB. These findings suggest that the increase in S. aureus and the enhancement of Th2 response induced by TBT exacerbate the AD-like lesions in mice treated with TNCB.

Animals↗
PubMed2002

Purification and identification of a tributyltin-binding protein from serum of Japanese flounder, Paralichthys olivaceus.

Tributyltin (TBT) is an industrial chemical used as an antifoulant in marine environments. Previously, we reported that TBT accumulates in the serum or plasma of some fishes and is bound to a high molecular weight compound in the serum of the Japanese flounder, Paralichthys olivaceus. In this study, we succeeded in purifying the TBT-binding protein (TBT-bp) from the serum of Japanese flounder by using gel filtration chromatography, anion exchange chromatography, and polyacrylamide gel electrophoresis, with a 2.6% yield and a 77-fold purification. The molecular mass of TBT-bp was approximately 46.5 kDa on sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and its isoelectric point was approximately 3.0 on isoelectric focusing-polyacrylamide gel electrophoresis. The TBT-bp contained 42% N-glycan. The cDNA nucleotide sequence of TBT-bp was determined by reverse transcription-polymerase chain reaction of Japanese flounder liver, and we deduced a sequence of 191 amino acids of mature TBT-bp. No sequence identical to the TBT-bp amino acid sequence was found within the SWISS-PROT (http://www.nig. ac.jp/) protein database; however, a lipocalin-like sequence pattern was observed. We concluded that the TBT-bp was a novel protein that has not yet been reported, although some DNA sequences from expressed sequence tags (ESTs) of Japanese flounder liver had a high identity. A high expression level of TBT-bp gene was found in the liver, but the gene was slightly detectable in the kidney and brain.

Amino Acid Sequence↗