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At least 865 records · Page 48Linked to original sources
PubMed1993

Organotins are co-clastogens in a whole mammalian system.

The frequency of micronuclei induced by mitomycin C (MMC) in mouse peripheral reticulocytes was enhanced by treatment with organotins: bis(tri-n-butyltin) oxide (TBTO) and triphenyltin chloride (TPTC). TBTO and TPTC did not themselves induce micronucleated reticulocytes (MNRETs) in mouse peripheral blood. When 50 mg/kg TBTO or 100 mg/kg TPTC was given orally to mice simultaneously with an intraperitoneal (i.p.) administration of 1 mg/kg MMC, however, TBTO and TPTC caused about 55% and 51% increases, respectively, in MMC-induced a synergistic MNRET frequency. Organotin administration 3 or 6 h before and 3 h after MMC injection also caused enhancement of MNRET frequency. These results demonstrate that TBTO and TPTC act as co-clastogens in a whole mammalian system.

Animals↗
PubMed1994

Antagonizing effect of triphenyltin chloride on cytosine-1-beta-D-arabinofuranoside potentiation of chromosome aberrations induced by mitomycin C.

We previously reported that the organotin triphenyltin chloride (TPTC), which has been widely used as an anti-fouling coating for fishing nets and ship bottoms, potentiated clastogen-induced chromosome aberrations during the G2 phase of the cell cycle. In this communication, CHO cells treated with mitomycin C (MMC) were post-treated with TPTC in the presence and absence of other agents--cytosine-1-beta-D-arabinofuranoside (araC), hydroxyurea, or caffeine--having a similar effect during the G2 phase of the cell cycle. The potentiating effect of araC was completely inhibited in the presence of TPTC at the concentration at which TPTC showed its potentiating effect, suggesting that potentiating effects of TPTC and araC are antagonistic. On the other hand, combined treatment with TPTC and caffeine or hydroxyurea showed a potentiating effect almost equal to the sum of the potentiating effects of each given separately.

Animals↗
PubMed1995

Biochemical analysis of recombinant glutathione S-transferase of Fasciola hepatica.

Four cDNAs encoding GST (rGST1, rGST7, rGST47 and rGST51) of Fasciola hepatica were expressed in Escherichia coli and the rGST proteins purified for biochemical analyses. The rGST proteins are 95% pure as indicated by Coomassie staining of proteins separated by SDS-PAGE. Molecular sieving by HPLC infers that, like the native protein, the rGST proteins form homodimers under non-denaturing conditions. The rGST proteins are recognised by antisera raised to the native GST of F. hepatica. All four rGST proteins from F. hepatica actively conjugate glutathione to the universal substrate, 1-chloro-2,4-dinitrobenzene. The activity of the rGSTs was also measured for substrates which have been shown to have partial specificity for the Alpha, Mu or Pi classes of mammalian GSTs (trans-4-phenyl-3-buten-2-one, ethacrynic acid), for substrates known to be products of lipid peroxidation (trans-2-nonenal, trans,trans-2,4-decadienal) and for epoxy-3-(p-nitrophenoxy)-propane (EPNP), a known substrate for the theta class of GST. No rGST were active with EPNP. rGST47 and 51 showed activity with the other four substrates. rGST7 was active with three substrates whereas rGST1 showed relatively low activity with all substrates except trans,trans-2,4-decadienal. The sensitivity of the rGST activity to inhibition by the GST inhibitors triphenyltin chloride and bromosulphophthalein also varied among the rGSTs with rGST1 showing a 800-fold difference in sensitivity between the inhibitors. These results show that F. hepatica expresses a family of GST isoenzymes which exhibit unique substrate and inhibitor profiles.

Amino Acid Sequence↗
PubMed1986

Suppression of thymocyte proliferation in vitro by a dioctyltin dichloride-induced serum factor.

Oral administration of dioctyltin dichloride (DOTC) results in the production or release of factors which appear to prevent thymocyte maturation at an early stage. Sera obtained from rats gavaged with 75 mg DOTC/kg on alternate days, significantly inhibited PHA-induced blastogenesis of normal thymocytes. In vitro uptake of tritiated thymidine by thymocytes obtained from DOTC-gavaged rats was markedly reduced. These events occurred 24 to 72 h after commencement of DOTC treatment and preceded overt thymic weight loss. The effects of DOTC may therefore be a consequence of factor(s) capable of blocking the intrathymic differentiation of T cell precursors.

Animals↗
PubMed1989

Cellular and molecular effects of di-n-octyltin dichloride on the rat thymus.

Experiments have been performed to characterise early changes in the proliferative capacity and phenotypic makeup of thymocytes obtained from DOTC-treated PVG rats. The analysis of density gradient-separated thymocytes demonstrated that within 72 h of oral dosing, spontaneous in vitro thymocyte proliferation was markedly suppressed. A concomitant depletion of an MRC OX18 positive thymocyte population was also observed. These events occurred prior to both overt thymic weight loss and characteristic, treatment-induced histopathological changes. Since recent evidences suggest that the growth factor interleukin-2 (IL-2) may play an important role in thymocyte proliferation, additional molecular biological studies were performed to evaluate whether DOTC may exert its anti-proliferative effects by compromising IL-2 production. Using a mRNA cytoplasmic dot blot technique, the examination of thymocyte lysates from treated and control animals revealed that DOTC markedly down regulated and at high doses abolished, the normal expression of the IL-2 gene. The high turnover gene alpha-actin was, however, unaffected by its action, thus demonstrating the selective effects of DOTC.

Animals↗
PubMed1984

Tin--a toxic heavy metal? A review of the literature.

A tolerable limit for tin concentration in canned food of 250 ppm (Fritsch et al., 1977) is generally accepted. However, biochemical effects attributable to tin have been observed even after oral administration of 1 and 3 mg Sn/kg body wt (Yamaguchi et al., 1980). These doses reflect 10 and 30 ppm tin in the diet. The experiments of de Groot (1973) showed that hemoglobin concentrations in the blood of rats decreased significantly feeding a diet containing 150 ppm tin. The absorption of iron was diminished after simultaneous administration of 0.8 mumol Sn(II) and iron, reflecting a tin dose of 95 ppm tin, by injection into jejunal loops of rats (Schäfer and Forth, 1983). In general, however, canned food usually plays a secondary role in daily nutrition. Fortunately, concentrations of about 2000 ppm tin as reported by Warburton et al. (1962) and Barker and Runte (1972) are not found in canned food, but values between 50 and 500 ppm are not unusual (Piscator, 1979). If a large amount of canned food is eaten daily over a long period, disturbances of gastric acid secretion and a reduction in iron absorption or heme metabolism cannot be excluded. The storage of food, especially acid foods, in opened cans should be avoided as this practice increases the amount of tin in the food when it is consumed.

Animals↗
PubMed1994

Enhanced teratogenic activity of di-n-butyltin diacetate by carbon tetrachloride pretreatment in rats.

Di-n-butyltin diacetate (DBTA) has been shown previously to cause malformations such as cleft mandible, ankyloglossia and fused ribs in rat foetuses after oral treatment of dams on day 8 of gestation. In this study, effects of pretreatment with carbon tetrachloride (CCl4) on the teratogenic activity of DBTA were examined in Wistar rats. Pregnant rats were pretreated sc with CCl4 (0.5 ml/kg) on days 6 and 7 of gestation and were treated orally with DBTA on day 8 of gestation at doses of 0, 4.5, 10 or 22 mg/kg. Caesarean sections were performed on day 20 of gestation, and foetuses were examined for external and skeletal anomalies. Pretreatment with CCl4 enhanced the incidence of external and skeletal malformations caused by DBTA. Concentrations of di-n-butyltin in embryos, maternal liver and maternal blood on day 9 of gestation were increased by CCl4 pretreatment, which inhibited the activity of maternal hepatic microsomal drug-metabolizing enzymes. These results suggest that there is little probability that metabolites of DBTA make a critical contribution to the teratogenicity of DBTA.

Abnormalities, Drug-Induced↗
PubMed1984

Effect of triphenyltin hydroxide on the immune system of the rat.

To evaluate the functional significance of triphenyltin hydroxide (TPTH)-induced lymphopenia and lymphocyte depletion in thymus-dependent areas of spleen and lymph nodes, various immune function studies were carried out after 3 or 4 weeks TPTH exposure. Weaned male rats were fed a diet containing 25 mg TPTH/kg, a concentration that did not influence food intake and weight gain. TBTO exposure was continued during the course of the function tests. As parameters of the cell-mediated immunity in 2 experiments the delayed-type hypersensitivity reactions to ovalbumin and tuberculin were significantly suppressed. No effect was observed on allograft rejection, splenic clearance of Listeria monocytogenes at days 5 and 6 after infection, and responsiveness of thymocytes to different T-cell mitogens. In contrast, the response of splenic lymphocytes to the T-cell mitogen phytohaemagglutinin was significantly suppressed. As TPTH treatment reduced the number of spleen cells, mitogenic response calculated per whole spleen was significantly depressed. Regarding the humoral immunity, no effect was observed on serum IgM and IgG levels, on the thymus-independent IgM response to E. coli lipopolysaccharide (LPS), and on the primary and secondary IgM and IgG response to the thymus-dependent antigen tetanus toxoid. Also, no effect was found on phagocytic and killing capacity of macrophages as demonstrated by unaltered splenic clearance of L. monocytogenes at days 1 and 2 after infection. Slightly enhanced mortality of TPTH-treated animals was observed in a L. monocytogenes mortality assay. Finally, TPTH did not increase the susceptibility of rats to endotoxin (LPS).

Animals↗
PubMed1987

The absorption, tissue distribution and excretion of di-n-octyltin dichloride in rats.

In this study the absorption, tissue distribution and excretion of 14C-labeled di-n-octyltin dichloride ([14C]DOTC) in rats were investigated after oral and intravenous (i.v.) administration. Although after i.v. administration with 1.2 mg [14C]DOTC/kg body weight the tissue radioactivity was about 3-4 times higher than after oral administration with 6.3 mg [14C]DOTC/kg body weight, the relative tissue accumulation was found to be the same after the oral and i.v. dosage. The highest amount of radioactivity was found in liver and kidney, and to a lesser degree in adrenal, pituitary and thyroid glands. The lowest activity was recovered from blood and brain. No selective accumulation was observed in thymus, although it has been reported that thymus atrophy is the most sensitive parameter of DOTC toxicity in rats. For all tissues a time dependent decrease in radioactivity was found, except for kidney. The excretion of radioactivity in feces and urine was determined after a single i.v. or oral dose of 1.2 and 2 mg [14C]DOTC, respectively. After i.v. administration most of the radioactivity was excreted in the feces which was characterized by a biphasic excretion pattern. In orally treated rats more than 80% of the radioactivity was already excreted in the feces during the first day after administration. This indicated that only a small part of the DOTC was absorbed, which was calculated to be approximately 20% of the dose. Similar half-life values of 8.3 and 8.9 days were obtained from the fecal excretion of radioactivity after the i.v. and oral administration, respectively. The urinary excretion of radioactivity appeared to be independent of the body burden, since the daily amount of radioactivity excreted in urine was nearly the same independent of the route of administration as well as the time after administration.

Absorption↗
PubMed1992

Susceptible period for the teratogenicity of di-n-butyltin dichloride in rats.

Pregnant rats were given di-n-butyltin dichloride (DBT) by gastric intubation at a dose of 20 mg/kg on days 7-9, 10-12 or 13-15 of pregnancy or at a dose of 20 or 40 mg/kg on day 6, 7, 8 or 9 of pregnancy. While treatment with DBT on days 7-9 was significantly and highly teratogenic, no evidence of teratogenicity was detected when DBT was given on days 10-12 or 13-15. Treatment on day 7 or 8 with both doses of DBT, but neither on day 6 or 9, resulted in an increased incidence of fetuses with malformations. The highest incidence of malformed fetuses occurred after treatment on day 8. The incidence of malformed fetuses was proportional to the dose of DBT. Anomaly of tail, anal atresia, club foot, omphalocele, deformity of the vertebral column, defect of the ribs and anophthalmia or microphthalmia were predominantly observed. It could be concluded that, following maternal exposure to DBT in rats, developing offspring are not susceptible to teratogenic effects of DBT on day 6 and that day 7 is the earliest susceptible period, day 8 is the highest susceptible period and day 9 is no longer a susceptible period for teratogenesis of DBT.

Animals↗
PubMed1983

Effect of dibutyltin dichloride on incidence of pancreatic adenocarcinoma induced in hamsters by a single dose of N-nitrosobis(2-oxopropyl)amine.

The effects of timing of a single intragastric application of dibutyltin dichloride, at a dosage of 30 mg/kg body wt, on N-nitrosobis(2-oxopropyl)amine (BOP)-induced pancreatic carcinomas have been studied in female Syrian golden hamsters. Dibutyltin dichloride, which has been shown to produce selected bile duct injury, was administered either 1 week before or 1 week after a single injection of BOP (20 mg/kg body wt). Control hamsters were injected with BOP alone or were given dibutyltin dichloride alone. The incidence of ductal adenocarcinomas strikingly decreased in hamsters when dibutyltin dichloride was ingested after BOP treatment, but remained unaffected when dibutyltin dichloride was given before carcinogen treatment. Two cases of sarcoma were observed in the group treated with dibutyltin dichloride before BOP injection. The incidence of insulomas, which were considered as spontaneous tumors, was not influenced by dibutyltin dichloride. These results showed that intragastric application of dibutyltin dichloride after BOP treatment significantly reduced the induction of pancreatic cancer. These findings do not support speculations based on epidemiologic studies as to a promoting effect of cholestasis.

Animals↗
PubMed1983

Antitumor activity of some diorganotin and tin(IV) complexes of Schiff bases.

Some new di-n-butyltin and tin(IV) complexes of the type Bu2SnL, Bu2SnL2 and SnL2 (where L = anions of Schiff bases derived from S-substituted dithiocarbazates and fluoro-aniline) have been prepared and screened for their antitumor activity in P 388 Lymphocyte Leukaemia system. These complexes do not show any toxicity at low dose levels and display T/C values in the range 94-124. Di-n-butyltin complex derived from salicylaldehyde-S-methyl dithiocarbazate has been found to be the most active in this series.

Animals↗
PubMed1990

Triphenyltin: a potent excitatory neurotoxicant. Its reciprocal effects on voltage-dependent Na and K currents of mammalian brain neuron.

Effects of triphenyltin (TPT) on voltage-dependent sodium current (INa) and two respective potassium currents (delayed and transient potassium currents, IKD and IA) were examined on hippocampal neurons acutely isolated from Wistar rats using a conventional suction pipette technique. TPT at concentrations of 10(-7) to 10(-5) M increased the peak amplitude of INa associated with a prolongation of current decay. On the other hand, TPT started to reduce the peak amplitude of IA at 10(-7) M and completely suppressed it at 10(-5) M or less. The peak amplitude of IKD was also reduced by TPT at 10(-6) M or more. Results suggest that TPT possesses an excitatory neurotoxic action and that TPT as a possible environmental hazard may be harmful for human health.

Animals↗
PubMed1986

Strain and sex differences in susceptibility of rats to dioctyltin dichloride.

Treatment with dioctyltin dichloride (DOTC) induced increased mortality, atrophy of the thymus and suppression of responses to concanavalin A. Brown Norway (BN) rats were more susceptible than Lewis (LEW) to the lethal effects of DOTC and males were more susceptible than females. Increased mortality did not correlate with changes in the histological appearance of the thymus. LEW X BN F1 hybrids resembled the LEW parent in susceptibility to the lethal effects of DOTC and the BN parent in susceptibility to changes in the thymus.

Animals↗
PubMed1990

Lack of covalent binding to DNA of di-n-octyltin dichloride (DOTC) in vivo and in vitro.

[14C]Di-n-octyltin dichloride ([14C]DOTC) was administered by oral gavage to male and female rats. After 96 h hepatic and thymic DNA was isolated. All DNA fractions were radioactive, but analysis of DNA hydrolysates by HPLC revealed that the radioactivity was incorporated via biosynthesis and was not due to adduct formation. The limit of detection for adduct formation, expressed in units of the covalent binding index (CBI = mumol chemical bound per mol nucleotides/mmol chemical applied per kg body wt.) was approximately 0.2 for liver DNA and about 0.7 for thymus DNA. This maximum possible DNA-binding ability is about 30,000 times lower than the corresponding value for the strong carcinogen, aflatoxin B1. In addition, [14C]DOTC did not bind covalently to calf thymus DNA in the presence or absence of rat liver S9 or to DNA of V79 Chinese hamster cells. This study therefore gives no indication for genotoxic activity of DOTC mediated by DNA binding.

Animals↗
PubMed1990

In vivo effects of di-n-butyltin dichloride on some enzymes and lipids of rat liver plasma membrane.

The in vivo effects of di-n-butyltin dichloride (DBT) on the enzyme activity and lipid constituents of liver plasma membrane were studied in male Albino rats. The rats were intraperitoneally administered with 0.1 ml (10% v/v) ethanol either alone or containing DBT (10 or 30 mg/kg/d) for 7 consecutive days. A significant inhibition of plasma membrane marker enzymes such as 5'-nucleotidase, gamma-glutamyltranspeptidase, alkaline phosphatase, Mg2(+)-ATPase, Na+/K(+)-ATPase and Ca2(+)-ATPase occurred in DBT-treated rats when compared with respective controls. Other important bioconstituents such as sialic acid and total phospholipid/cholesterol ratio were also significantly decreased in DBT-treated rats when compared with corresponding controls. These results suggest that interaction of DBT with liver plasma membrane constituents might cause derangement of its structural and functional organization, thus leading to hepatotoxicity.

5'-Nucleotidase↗
PubMed1991

Teratogenicity of di-n-butyltin dichloride in rats.

Pregnant rats were given di-n-butyltin dichloride (DBT) by gastric intubation at a dose of 0, 2.5, 5.0, 7.5 or 10.0 mg/kg on days 7-15 of pregnancy. Maternal toxicity occurred in the 7.5 and 10.0 mg/kg groups as evidenced by a significant increase in maternal death and decrease in food consumption and body weight gain. The incidence of fetuses with malformations was roughly proportional to the dose of DBT, and was significantly increased in the 5.0, 7.5 and 10.0 mg/kg groups. Cleft jaw, ankyloglossia, defects of the mandible, fusion of the ribs and deformity of the vertebral column were predominantly found. It is concluded that DBT produced teratogenic effects in the absence of maternal toxicity.

Abnormalities, Drug-Induced↗