Abstract 4319: Effects of chemotherapeutics on organotypic corticostriatal slice cultures identified by a new panel of fluorescent and immunohistochemical markers

Abstract

Effects of chemotherapeutics on glioma cell lines and spheroids are usually investigated without evaluating the effects of even very high concentrations of chemotherapeutics on normal brain tissue. To perform such investigations, the aim of the present study was to establish a panel of markers for detection of general cell death and more specific neuronal and glial degeneration induced by chemotherapeutics in organotypic rat corticostriatal slice cultures. Organotypic rat corticostriatal slice cultures were exposed to the alkylating agents temozolomide and nimustine, the tyrosine kinase inhibitor imatinib mesylate and the microtubule destabilizing agent vincristine. Densitometric measurements of uptake of the fluorescent dye propidium iodide were used for quantifying cellular degeneration. Moreover, paraffin sections were HE stained and immunohistochemically stained for the neuronal marker MAP2, the astroglial marker GFAP, and the oligodendrocyte marker p25α. The results showed that clinical drug concentrations were non-toxic. However, a time dependent increase in PI uptake was observed for supratherapeutic concentrations of the drugs, except for temozolomide, where no toxicity was observed at all. Corresponding immunostaining showed loss of MAP2 staining and increased expression of GFAP and p25α for cultures exposed to 1000 nM vincristine. Cultures exposed to supratherapeutic concentrations of nimustine and imatinib mesylate disintegrated, leaving no tissue for histology. In conclusion, corticostriatal slice cultures and the established panel of markers represent an excellent tool for detecting toxicity by chemotherapeutics. Toxicity was not detected at clinical concentrations, but high concentrations with toxic effects were identified suggesting that some of the earlier identified anti-cancer effects in the literature are general cytotoxic effects and not specific anti-cancer effects. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4319. doi:10.1158/1538-7445.AM2011-4319