Modulation of the DNA repair system and ATR-p53 mediated apoptosis is relevant for tributyltininduced genotoxic effects in human hepatoma G2 cells

The toxic effects of tributyltin (TBT) have been extensively documented in several types of cells, but the molecular mechanisms related to the genotoxic effects of TBT have still not been fully elucidated. Our study showed that exposure of human hepatoma G2 cells to 1-4 μmol/L TBT for 3 hr caused severe DNA damage in a concentration-dependent manner. Moreover, the expression levels of key DNA damage sensor genes such as the replication factor C, proliferating cell nuclear antigen and poly (ADP-ribose) polymerase-1 were inhabited in a concentration-dependent manner. We further demonstrated that TBT induced cell apoptosis via the p53-mediated pathway, which was most likely activated by the ataxia telangiectasia mutated and rad-3 related (ATR) protein kinase. The results also showed that cytochrome c, caspase-3, caspase-8, caspase-9, and the B-cell lymphoma 2 were involved in this process. Taken together, we demonstrated for the first time that the inhibition of the DNA repair system might be more responsible for TBT-induced genotoxic effects in cells. Then the generated DNA damage induced by TBT initiated ATR-p53-mediated apoptosis.     

Tributyltin chloride results in dorsal curvature in embryo development of Sebastiscus marmoratus via apoptosis pathway

Tributyltin (TBT) is a ubiquitous marine environmental contaminant characterized primarily by its reproductive toxicity. However, the embryotoxicity of TBT has not been extensively described, especially in fishes. The aim of this study was to investigate the developmental toxicity of waterborne TBT at environmental levels (0, 0.1, 1, and 10 ng L⁻¹ as Sn) on Sebastiscus marmoratus embryos. Our study showed that TBT reduced the hatchability and caused apparent morphological abnormalities including dorsal curvature, severely twisted tails and pericardial edema. In addition, localized apoptosis was found in the tail regions of embryos after TBT exposure. The study provided a possible mechanistic link between apoptosis and TBT-induced twisted tails abnormality. TBT exposure induced retinoid X receptor α expression in S. marmoratus embryos at the 0.1 and 1 ng L⁻¹ group, which would be responsible for the increasing apoptotic cells induced by TBT. The results of the present study have widespread implications for environmental ecological assessment, management and the etiology of developmental defects.     

Genotoxic effects of binary mixtures of xenoandrogens (tributyltin, triphenyltin) and a xenoestrogen (ethinylestradiol) in a partial life-cycle test with Zebrafish (Danio rerio)

A partial life-cycle test with the model fish Danio rerio was performed in order to evaluate the genotoxic potential of binary mixtures of xenoandrogenic (tributyltin--TBT; triphenyltin--TPT) and an estrogenic compound (ethinylestradiol--EE2). Five days post-fertilisation larvae were diet-exposed to environmental relevant concentrations of TBT and TPT (25 ng/g-100 ng/g), and water-exposed to ethinylestradiol (3.5 ng/L) for a four-month period; binary mixtures of TBT plus EE2 and TPT plus EE2 were run in parallel. The erythrocytic nuclear abnormalities (ENA) assay in circulating erythrocytes was used to evaluate genotoxicity in the end of the four-month exposure period. A significant increase (p<0.05, Kruskall-Wallis non-parametric ANOVA) in ENA frequency, in comparison with control animals, was observed in those animals exposed to TBT and TPT (the highest doses only), and to EE2 and the binary mixtures, although neither synergistic nor additive effects of the tested compounds were evident. Overall, the results clearly indicate that chronic exposure to low levels of TBT, TPT, EE2 and binary mixtures of TBT plus EE2 and TPT plus EE2 are genotoxic to zebrafish, which may suggest that wild fish populations may be under increased DNA damage in areas contaminated by these endocrine disrupting chemicals.     

Tributyltin pollution in sediments from Alexandria's coastal areas

Presence of Tributyltin (TBT) in Alexandria’s coastal water areas has been demonstrated by measuring concentrations of this compound. The TBT was measured in sediments from three docking areas namely: Western Harbour, Eastern Harbour and Abu Qir Bay. The sediment of those areas has been affected by marine traffic and other industrial activities. This is reflected by the distribution of TBT in the sediments nearby the shipyards in the three docking areas of the region where the average values of 258.6 ηg TBT/g for Western Harbour; 126.4 ηg TBT/g dw for Abu Qir Bay and 42.3 ηg TBT/g dw for the Eastern Harbour were recorded. This fact reflects the effect of industry and marine traffic on the marine environments of the Alexandria region.     

Butyltin Compounds in Sediments of the Bahía Blanca Estuary, Argentina

Systematic measurements of both Tributyltin (TBT) and Dibutyltin (DBT) in sediments along different locations in the inner zone of Bahía Blanca estuary were done. Two samples were taken near the main dry dock facility, at Puerto Belgrano naval base, in Argentina. TBT concentrations from non-detected to 170.3 ng Sn g⁻¹ were measured in the inner region of the estuary, and higher one of 3,288 ng Sn g⁻¹ near the dry dock at Puerto Belgrano. DBT values ranging between non-detected and 75.2 ng Sn g⁻¹ were obtained along the principal channel, but extreme concentration of 1,645 ng Sn g⁻¹ was measured at Puerto Belgrano. These values show that this estuary is affected by organotin pollution, mainly in areas of heavy shipyard activities.     

海洋环境中的三丁基锡污染

介绍了三丁基锡的性质，从化学分析、环境水平、毒性和人体接触等方面回顾了海洋环境中三丁基锡的研究进展。指出从食物中摄取是人类接触三丁基锡化合物的主要途径，提出对实验毒性、饮食摄入、人类健康潜在影响开展调查，以及发展新的消除三丁基锡的技术很有必要。