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Cytotoxicity of organotin compounds in different cultured cell lines

Institute of Experimental and Clinical Pharmacology and Toxicology, University of Lübeck, Ratzeburger Allee 160, 23538 Lübeck, Germany

Reiner Johannisson

Institute of Pathology, University of Lübeck, Ratzeburger Allee 160, 23538 Lübeck, Germany

Sarwar Syed Ali

Institute of Experimental and Clinical Pharmacology and Toxicology, University of Lübeck, Ratzeburger Allee 160, 23538 Lübeck, Germany

Johannes Schulze

Office of the Dean, Johann Wolfgang Goethe-University Theodor Stern-Kai 7, 60590 Frankfurt/Main, Germany

Claus-Peter Siegers

Institute of Experimental and Clinical Pharmacology and Toxicology, University of Lübeck, Ratzeburger Allee 160, 23538 Lübeck, Germany, siegers{at}medinf.mu-luebeck.de

Organotin as monobutyltin (MBT), dibutyltin (DBT) and tributyltin (TBT) compounds are used as fungicides and anti-fouling compounds; small amounts are added to the new European Euro bills. Little is known about the toxicological profile of these compounds uptake and metabolism. We, therefore, studied the cytotoxicity of these agents in different cell lines, i.e., liver HepG2, renal LLCMK2 and ocular CEC cells. As a measure of cell growth and death, the neutral red assay and the release of LDH into the medium were used. IC₅₀ values for growth inhibition by TBT were calculated as 160 nM in LLC-MK2, 150 nM in HepG2 and 180 nM in CEC cells; for DBT the corresponding values were higher, i.e., 500 nM DBT for LLC-MK2 cells, 300 nM for HepG2 cells and 220 nM for CE cells. ED₅₀ values for LDH release indicating disturbances of the outer cell membrane was > 250 nM for TBT and > 350 nM for DBT in all cells. MBT was not toxic in concentrations up to 500 nM. Electron microscopic studies of cells treated with 300 nM tributyltin indicated severe mitochondrial damage with much less effect seen in other cell structures. We conclude that no differences exist between different cell lines that may serve as examples of tissues relevant for organotin exposure (eye), metabolism (liver) and specific metalloid damage (kidney). Growth inhibition was affected at organotin concentrations between 150 and 500 nM. This concentration is approximately 70-200 fold higher than values estimated in environmental samples.

Key Words: cell culture • cytotoxicity • histology • organotin

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