UPTAKE AND CYTOTOXICITY OF 9-METHOXY-N-2-METHYLELLIPTICINIUM ACETATE IN HUMAN BRAIN AND NON-BRAIN TUMOR-CELL LINES

9-Methoxy-N-2-methylellipticinium acetate (MMEA) was preferentially cy totoxic to human brain tumor cell lines in the in vitro primary screen of the U.S. National Cancer Institute. In the present study, the aver age intracellular accumulation of radioactivity derived from [C-14]MME A concentrations that were selectively cytotoxic to sensitive brain tu mor cell lines was nearly 4-fold greater than in human rumor cell line s derived from the lung, kidney, ovary and colon. The extent of peak c ellular accumulation of [C-14]MMEA-derived radioactivity, achieved aft er 10-15 hr of drug exposure, was correlated positively with relative MMEA cytotoxicity in brain tumor cell lines (r(2) = 0.963). A similar correlation (r(2) = 0.967) was observed in selected non-brain tumor ce ll lines but required substantially higher (18-fold) concentrations of MMEA. [C-14]MMEA radioactivity accumulation by a selected glioblastom a cell line occurred via an energy-requiring system that was predomina ntly sodium and pH independent.