• Proceedings of the Korean Society of Toxicology Conference
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• 2002.11b
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• pp.168-168
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• 2002

A clear association between occupational tributyltin (TBT) exposure and testicular cell line, TM3 has been observed in mouse. In the present study, we have investigated cytotoxic effects of TBT on Significant cytolethality was observed in TM3 cells in a time- and concentration-dependent manner when measured by MTT assays. (omitted)

• Proceedings of the Korean Society of Toxicology Conference
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• 2003.10b
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• pp.138-138
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• 2003

Tributyltin (TBT) is also recognized as an endocrine disrupter. Organotin compounds such as TBT are widely used as agricultural biocides, and for antifouling paint of ship bottoms and of fishing nets. In this study, we investigated the role of nur 77 in induction of apoptosis in TBT-induced leydig cells.(omitted)

• Korean Journal of Environmental Biology
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• v.21 no.3
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• pp.303-307
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• 2003

Tributyltin (TBT) used world-wide in antifouling paints toy ships is a wide-spread environmental pollutant. At low doses, antiproliferative modes of action have been shown to be involved, whereas at higher doses apoptosis seems to be the mechanism of toxicity in reproductive organs by TBT. In this study, we investigated that the mechanisms underlying apoptosis induced by TBT in R2C cell. Effects of TBT on intracellular $Ca^{2+}$ level and reactive oxygen species (ROS) were investigated in R2C cells by fluorescence detector. TBT significantly induced intracellular $Ca^{2+}$ level in a time-dependent manner. The rise in intracellular $Ca^{2+}$ level was followed by a time-dependent generation of reactive oxygen species (ROS) at the cytosol level. Simultaneously, TBT induced the release of cytochrome c from the mitochondrial membrane into the cytosol. Furthermore, ROS production and the release of cytochrome c were reduced by BAPTA, an intracellular $Ca^{2+}$ chelator, indicating the important role of $Ca^{2+}$ in R2C during these early intracellular events. In addition, Z-DEVD FMB, a caspase -3 inhibitor, decreased apoptosis by TBT. Taken together, the present results indicated that the apoptotic pathway by TBT might start with an increase in intracellular $Ca^{2+}$ level, continues with release of ROS and cytochrome c from mitochondria, activation of caspases, and finally results in DNA fragmentation.

• Development and Reproduction
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• v.15 no.4
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• pp.373-383
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• 2011

Tributyltin (TBT) is one of endocrine disrupters which are known as having similar function to sex steroid hormone inducing apoptosis in various tissues of rodents. Recently, it has been reported that TBT induces apoptosis in thymus causing the decreased thymic function, but little is known about the mechanism. To elucidate the mechanism, three-week-old SD female rats were orally administrated with TBT 1, 10, and 25 mg per body weight (kg) and sesame oil as a control for 7 days. On day 8, the thymi were obtained and weighed, and then the number of thymocytes was counted. We also performed H&E staining, TUNEL assay, and Annexin V flow cytometric analysis to examine the apoptosis rates and the structure in the thymus. Next, we investigated the adipogenesis and apoptosis-related mRNA expression levels in the thymi by real-time PCR. The thymic weight and the number of thymocytes were decreased by TBT in a dose-dependent manner. As a result of the H&E staining, the boundary between cortical and medullary area was blurred in the thymi of TBT treated rats compared to those of controls. In the results of TUNEL assay and Annexin V flow cytometric analysis, apoptosis rates in the thymus were increased after TBT treatment. The expression levels of thymic epithelial cell marker genes such as EVA, KGF, AIRE, and IL-7 were significantly decreased in the thymi of TBT treated rats, but $PPAR{\gamma}$, aP2, PEPCK, and CD36 were significantly increased. The expression of $TNF{\alpha}$ and TNFR1 as apoptosis-related genes also was significantly increased after TBT treatment. The present study demonstrates that TBT can increase the expression of adipogenesis and apoptosis-related genes leading to apoptosis in the thymus. These results suggest that the increased adipogenesis of thymus by TBT exposure might induce apoptosis in the thymus resulting in a loss in thymic immune function.

• Fisheries and Aquatic Sciences
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• v.9 no.2
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• pp.64-69
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• 2006

Cytochrome P450 (CYP1A) gene expression in the liver and sex steroid levels in plasma were investigated in olive flounder (Paralichthys olivaceus) exposed to tributyltin (TBT) and benzo[a]pyrene (BaP). We constructed a cDNA library and cloned a 230-base sequence encoding partial CYP1A DNA. The CYP1A gene expression level was estimated using northern blotting. Hepatic CYP1A mRNA levels in fish injected with BaP at 10 mg/kg body weight (b.w.) increased for 48 h after injection. However, fish injected with both BaP and TBT at 10 mg/kg b.w. showed no significant changes in CYP1A mRNA level after 48 h. Plasma concentrations of testosterone and $17{\beta}$-estradiol were not significantly different in males and females injected with BaP and TBT. We suggest that TBT-induced suppression of BaP bioactivity should be interpreted with caution in biomonitoring field studies.

• Korean Journal of Fisheries and Aquatic Sciences
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• v.34 no.6
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• pp.584-587
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• 2001

The effects of tributyltin (TBT), triphenyltin (TPhT) and Aroclor 1254 on germinal vesicle breakdown (GVBD) and ovulation of olive flounder (Paralichthys olivaceus) were investigated in in vitro bioassay. TBT, TPhT and Aroclor 1254 showed the inhibition effects on GVBD and ovulation in response to HCG. The oocyte response appeared to be more sensitive to TBT than Aroclor 1254. TBT was more effective in inhibition GVBD at concentrations of 0.1 and 1 ppm. However, no significant inhibition was obseued in concentrations tested ($0.0001\~1\;ppm$). Significant inhibition of ovulation in response to HCG occurred at TBT (0.01, 0.1, 1 ppm), TPhT (0.01, 0.1, 1 ppm) and Aroclor 1254 (0.01, 1 ppm, except 0,1 ppm), compared to HCG control, The lowest ovulation rate was measured at 1 ppm TBT, These data suggest that TBT (or TPhT) could possibly interfere the actions of progestogens to induce GVBD and ovulation in in vitro bioassay system.

• Analytical Science and Technology
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• v.14 no.2
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• pp.115-122
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• 2001

Butyltin compounds, including mono-(MBT), di-(DBT) and tributyltin(TBT) were analyzed in 44 human blood samples randomly collected from a hospital in "K" a city. Gas chromatograph equipped with flame photometric detector(FPD) was used to quantify the amounts of butylin compounds. Method detection limits(MDL) of this analytical method were 3.69ng Sn/g for MBT, 0.91ng Sn/g for DBT and 1.09ng Sn/g wet wt for TBT respectively. Standard reference material(SRM) containing of $1.3{\mu}g/g$ TBT as chloride was analyzed to check if this analytical results would be reliable. Recovery of about 90% was obtained through this analysis, indicating that the analytical method from butyltin compounds blood was reliable. The concentrations of butyltin compounds ranged MDL(<3.69) to 7.93ng Sn/g for MBT and 1.15 to 5.41ng Sn/g wet wt for DBT. Tributyltin was below detection limit in all samples. Detection limits of our results are lower than those reported by Kannan et al. who reported butyltin compounds in 33 human blood samples in the United States. Detection of MBT and DBT on blood sample implies that butyltin compounds could be absorbed through consumption of seafoods or exposure to food stuffs made of plastics and household items. Further study is needed to examine if butyltin compounds in blood can be reliably analyzed and used as intake index.

• Korean Journal of Fisheries and Aquatic Sciences
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• v.30 no.6
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• pp.923-928
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• 1997

The occurrence of butyltin compounds in the seawater and sediment of Masan Bay was investigated. The concentrations were in the range of $ND-0.059{\mu}g/\ell$ for tributyltin (TBT), $ND-0.091{\mu}g/\ell$ for dibutyltin (DBT) and $ND-0.720{\mu}g/\ell$ for monobutyltin (MBT) in the seawater, and $ND-0.233{\mu}g\;TBT/g.dry$, $ND-0.197{\mu}g-DBT/g.dry$ and $ND-0.684{\mu}g-MBT/g.dry$ in the sediment. Among the butyltin compounds, the major component in the seawater was MBT, while the predominant species in the sediment changed with time. The tributyltin concentrations in the sediment are approximately three orders of magnitude greater than the associated water column levels. Sediment/water partition coefficients (K) of TBT were between $0.6\times10^3\;and\;5.0\times10^3$.

• Development and Reproduction
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• v.14 no.4
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• pp.297-306
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• 2010

Tributyltin (TBT), an endocrine disrupting chemical, has been reported to decrease testicular function by causing apoptosis in the testis, but this mechanism is not fully understood. Thus, in this study we examined whether TBT induces adipogenesis of the Leydig cells to find out the correlation between adipogenesis and apoptosis in the testis. Three week old SD male rats were orally administrated with sesame oil, 1 mg/kg of TBT, or 10 mg/kg of TBT daily for 1 week and weighed after administration. The testes obtained on day 8 were weighed and stained with BODIPY and TUNEL kit. Using total RNA extracted from the isolated Leydig cells, adipogenesis and apoptosis-related genes were analyzed by real-time PCR. The testicular weights of the rats treated with 10 mg/kg TBT were significantly decreased compared to those in the control rats treated with sesame oil. As a result of BODIPY staining, the number of Leydig cells stained with BODIPY was increased in the rats treated with 10 mg/kg TBT compared with the control rats. Similar to BODIPY staining results, the TUNEL assay showed that the apoptosis of Leydig cells was increased in TBT treated rats. The results of the gene expression analysis in the Leydig cells showed that the expression of adipogenesis-related genes (PPAR${\gamma}$, aP2, Perilipin, CD36) and apoptosis-related genes (TNFRSF1A, TNFSF10) was increased after TBT administration. The present study demonstrates that TBT induces the expression of adipogenesis-related and apoptosis-related genes in the Leydig cells leading to adipogenesis and apoptosis in the testes. These results suggest that the dysfunction of Leydig cells by TBT exposure may cause a loss in testicular function.

• Proceedings of the Korean Society of Toxicology Conference
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• 2003.05a
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• pp.68-69
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• 2003

Tributyltin (TBT) used world-wide in antifouling paints for ships is a widespread environmental pollutant and cause reproductive organs atrophy in rodents. At low doses, antiproliferative modes of action have been shown to be involved, whereas at higher doses apoptosis seems to be the mechanism of toxicity in reproductive organs by TBT. (omitted)