HISTOLOGICAL, HISTOCHEMICAL AND AUTORADIOGRAPHIC EVIDENCE OF IN-VITRONEUROTOXIC EFFECTS OF THE NOVEL ANTITUMOR AGENT, 9-METHOXY-N-2-METHYLELLIPTICINIUM ACETATE

9-Methoxy-N-2-methylellipticinium acetate (MMEA) exhibits selective cy totoxicity towards glial-derived human brain tumor cell lines comprisi ng the U.S. National Cancer Institute preclinical drug screen. Neuroto xic potential of MMEA has been demonstrated in an in vitro model emplo ying sagittal slices of rat brain. Histochemical staining of rat brain slices for lactate dehydrogenase (LDH) activity revealed decreased st aining intensity following incubation with increasing concentrations o f MMEA (0.1 - 100 mu M). Cytological evaluation of paraffin sections s tained with Cresyl Fast Violet revealed neuronal damage delineated by cytoplasmic vacuolation, and distention and fraying of the plasma memb rane. No glial or vascular pathology could be discerned. Autoradiograp hy, following exposure to C-14-MMEA, revealed distinct labelling of th e large neurons of the brain stem, neurons in the thalamus and pyramid al neurons of the hippocampus, indicating neuronal uptake of the drug. (C) 1997 Intox Press, Inc.