Membrane lesions in cultured mouse neuroblastoma cells exposed to metal compounds

Tritiated 2-deoxy-D-glucose (dGlc) was rapidly taken up into cultured mouse neuroblastoma C1300 cells (clone 41A3). Upon perfusion the preloaded cultures slowly released radioactivity as [3H] 2-deoxy-D-glucose-6-phosphate ([3H]dGlc-6-P) (rate const. = 0.017 min-1) from a pool corresponding to 74% (t1/2 = 41 min) of the total radioactivity incorporated. Destruction of the plasma membrane of the cells by means of Triton X-100 (1.0%) resulted in a rapid and total release of the radioactivity. CH3HgCl, HgCl2, (C2H5)3SnCl and K2Cr2O7 all caused an increase in the passive cell membrane permeability to [3H]dGlc-6-P. A membrane toxic concentration (MTC) was defined as the concentration of the tested metal compound giving rise to an increase in the relative efflux from 1.0 to 1.2 during 60 min perfusion. Using this MTC-value, the membrane toxicity of the compounds could be ranked in the following order: CH3HgCl (MTC = 9 x 10(-7) M) greater than HgCl2 (MTC = 6 x 10(-6) M) greater than (C2H5)3SnCl (MTC = 3 x 10(-4) M) greater than K2Cr2O7 (MTC = 7 x 10(-4) M). Since this differential toxicity is in accordance with other reports it is concluded that 2-deoxy-D-glucose (dGlc) may be used together with 41A3 cells to screen metal compounds for their membrane toxicity.