Subcellular distribution of titanium in the liver after treatment with the antitumor agent titanocene dichloride |
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Authors: | P Köpf-Maier R Martin |
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Institution: | 1. Institut für Anatomie, Freie Universit?t Berlin, K?nigin-Luise-Stra?e 15, D-1000, Berlin 33 2. Sektion Elektronenmikroskopie, Universit?t Ulm, Oberer Eselsberg, D-7900, Ulm/Donau, Federal Republic of Germany
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Abstract: | In the present study, the subcellular distribution of titanium in the liver of mice was determined 24 and 48 h after application
of a therapeutic (ED100; ED = effective dose) and a toxic (LD25; LD = lethal dose) dose (60 and 80 mg/kg, respectively) of the antitumor agent titanocene dichloride by electron spectroscopic
imaging at the ultrastructural level. At 24 h, titanium was mainly accumulated in the cytoplasm of endothelial and Kupffer
cells, lining the hepatic sinusoids. Titanium was detected in the nucleoli and the euchromatin of liver cells, packaged as
granules together with phosphorus and oxygen. One day later titanium was still present in cytoplasmic inclusions within endothelial
and Kupffer cells, whereas in hepatocyte nucleoli only a few deposits of titanium were observed at 48 h. At this time titanium
was mainly accumulated in the form of highly condensed granules in the euchromatin and the perinucleolar heterochromatin.
It was found in the cytoplasm of liver cells, incorporated into cytoplasmic inclusion bodies which probably represent lysosomes.
Sometimes these inclusions were situated near bile canaliculi and occasionally extruded their content into the lumen of bile
capillaries. This observation suggests a mainly biliary elimination of titanium-containing metabolites. These results confirm
electron spectroscopic imaging to be an appropriate method for determining the subcellular distribution of light and medium-weight
elements within biological tissues. Insights into the cellular mode of action of titanocene complexes or titanocene metabolites
can be deduced from the findings of the present study. |
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Keywords: | Electron spectroscopic imaging Subcellular distribution Liver Titanium Titanocene dichloride Antitumor agent |
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