274 Estramustine (EAM) induces apoptosis in malignant human and rat glioma but not in normal brain tissue

Abstract

Background EaM exerts a specific cytotoxicity in malignant glioma. The aim was to further characterise the effect of EaM, with special regards to the DNA damage. Methods A rat glioma model with BT4C cells was used. The animals were treated with EaM (20 mg/kg). Following 0.5 to 96 hrs specimens from the brain and tumour tissue were taken after a single dose (280 mg) EaM. In situ end labelling (ISEL), traditional morphology and agarosgels were used for detection of apoptotic cells. Resulrs In the rat tumour tissue an increase of ISEL positive cells was seen with a peak 4–8 hrs after EaM treatment. Thereafter only a few positive cells were seen. The gel analysis supported the observations. Apoptotic cells were also seen in human glioma. In normal tissue and untreated tumour, no apoptotic cells were observed. Conclusion EaM induces apoptosis in malignant rat glioma and most interesting also in the clinical situation but not in normal brain tissue. The clinical and therapeutic significance of the observation need to be further studied.