Transport and Binding of Mesoporphyrin IX by Leukemia L1210 Cells¹

The combination of mesoporphyrin IX and light is cytotoxic to leukemia L1210 cells, resulting in membrane damage and loss of viability. In this study, mesoporphyrin transport and the cellular environment of accumulated drug were examined. The latter was characterized by measurements of absorbance and fluorescence spectra and of effects of irradiation on subsequent capacity of cells for transport of the nonmetabolized amino acid cycloleucine. We observed a rapid accumulation of drug at a relatively hydrophilic cellular environment (dielectric constant, 20) from which light-catalyzed inhibition of cycloleucine transport was clearly demonstrable. Washing at 37° rapidly depleted this cellular region of drug. Longer incubations resulted in accumulation of porphyrin at more hydrophobic loci (dielectric constant, ∼10) from which the drug was not readily washed and from which the efficiency of light-catalyzed damage to membrane transport was relatively low. These findings are consistent with the hydrophobic nature of mesoporphyrin (octanol:water partition ratio, 10).