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Histological, Histochemical and Autoradiographic Evidence of in Vitro Neurotoxic Effects of the Novel Antitumor Agent, 9-Methoxy-N-2-Methylellipticinium Acetate

  1. Author:
    Shankar, L.
    Ravindranath, V.
    Boyd, M. R.
    Vistica, D. T.
    Shankar, S. K.

  2. Author Address

    Shankar SK NATL INST MENTAL HLTH & NEUROSCI DEPT NEUROPATHOL HOSUR RD BANGALORE 560029 KARNATAKA INDIA NATL INST MENTAL HLTH & NEUROSCI DEPT NEUROPATHOL BANGALORE 560029 KARNATAKA INDIA NATL INST MENTAL HLTH & NEUROSCI DEPT NEUROCHEM BANGALORE 560029 KARNATAKA INDIA NCI LAB DRUG DISCOVERY RES & DEV DEV THERAPEUT PROGRAM FREDERICK, MD 21702 USA
    1. Year: 1997
  2. Journal: Neurotoxicology
    1. 18
    2. 1
    3. Pages: 89-95
  4. Type of Article: Article
  1. Abstract:

    9-Methoxy-N-2-methylellipticinium acetate (MMEA) exhibits selective cytotoxicity towards glial-derived human brain tumor cell lines comprising the U.S. National Cancer Institute preclinical drug screen. Neurotoxic potential of MMEA has been demonstrated in an in vitro model employing sagittal slices of rat brain. Histochemical staining of rat brain slices for lactate dehydrogenase (LDH) activity revealed decreased staining intensity following incubation with increasing concentrations of MMEA (0.1 - 100 mu M). Cytological evaluation of paraffin sections stained with Cresyl Fast Violet revealed neuronal damage delineated by cytoplasmic vacuolation, and distention and fraying of the plasma membrane. No glial or vascular pathology could be discerned. Autoradiography, following exposure to C-14-MMEA, revealed distinct labelling of the large neurons of the brain stem, neurons in the thalamus and pyramidal neurons of the hippocampus, indicating neuronal uptake of the drug. (C) 1997 Intox Press, Inc. [References: 13]

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