The cytotoxicity of two recently synthesized triorganotin isothiocyanate derivatives, nuclear retinoid X receptor ligands, was tested and compared in estrogen-receptor-positive MCF 7 and -negative MDA-MB-231 human breast carcinoma cell lines. A 48 h MTT assay indicated that tributyltin isothiocyanate (TBT-ITC) is more cytotoxic than triphenyltin isothiocyanate (TPT-ITC) in MCF 7 cells, and the same trend was observed in the MDA-MB-231 cell line. A comet assay revealed the presence of both crosslinks and increasing DNA damage levels after the 17 h treatment with both derivatives. Differences in cytotoxicity of TBT-ITC and TPT-ITC detected by FDA staining correspond to the MTT data, communicating more pronounced effects in MCF 7 than in the MDA-MB-231 cell line. Both derivatives were found to cause apoptosis, as shown by the mitochondrial membrane potential (MMP) depolarization and caspase-3/7 activation. The onset of caspase activation correlated with MMP dissipation and the total cytotoxicity more than with the amount of active caspases. In conclusion, our data suggest that the DNA damage induced by TBT-ITC and TPT-ITC treatment could underlie their cytotoxicity in the cell lines studied.

• MeSH
• antitumorózní látky chemie   farmakologie   MeSH
• apoptóza účinky léků   MeSH
• isothiokyanatany chemie   farmakologie   MeSH
• lidé MeSH
• membránový potenciál mitochondrií účinky léků   MeSH
• MFC-7 buňky MeSH
• nádorové buněčné linie MeSH
• nádory prsu farmakoterapie   genetika   metabolismus   MeSH
• organocínové sloučeniny chemie   farmakologie   MeSH
• poškození DNA účinky léků   MeSH
• retinoidní X receptory metabolismus   MeSH
• trialkylcínové sloučeniny chemie   farmakologie   MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• srovnávací studie MeSH

The effect of long-term exposure to tributyltin (TBT) on the intestine-related biochemical biomarkers in common carp was investigated in this study. Fish were exposed at sub-lethal concentrations of TBT (75 ng/L, 0.75 and 7.5 μg/L) for 60 days. Multiple biomarkers were measured, including digestive enzymes (trypsin, lipase and amylase), antioxidant responses (malondialdehyde (MDA) and total antioxidative capacity (T-AOC)), RNA/DNA ratio and the expression of digestive-related genes (try, lipc and amy). TBT exposure at 0.75 and 7.5 μg/L led to significantly inhibited activities of all digestive enzymes. At higher concentration of TBT, oxidative stress was apparent as reflected by the significant higher MDA content in the fish intestine, associated with an inhibition of T-AOC activities. After 60 days, the RNA/DNA ratio in fish intestine was significantly lower in groups exposed to TBT at higher concentrations (0.75 and 7.5 μg/L). In addition, the expression levels of try, lipc and amy in intestine of all treated fish were inhibited, even at the environmental concentration (75 ng/L). Our results suggest that long-term exposure to TBT could result in different responses of intestine-related biochemical biomarkers in fish, which could be used as new potential indicators for monitoring residual TBT present in aquatic environment.

• MeSH
• antioxidancia metabolismus   MeSH
• biologické markery metabolismus   MeSH
• chymotrypsin metabolismus   MeSH
• DNA metabolismus   MeSH
• kapři metabolismus   MeSH
• malondialdehyd metabolismus   MeSH
• oxidační stres účinky léků   MeSH
• pankreatická elastasa metabolismus   MeSH
• pesticidy chemie   toxicita   MeSH
• RNA metabolismus   MeSH
• střeva účinky léků   metabolismus   MeSH
• trialkylcínové sloučeniny chemie   toxicita   MeSH
• trypsin metabolismus   MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH