A MODEL FOR CELLULAR UPTAKE AND INTRACELLULAR BEHAVIOR OF PARTICULATE-BOUND MICROPOLLUTANTS

The uptake and subsequent behaviour and toxicity of organic micropollu tants in organisms is governed by the physical chemical speciation of these contaminants. Since lipophilic pollutants are largely bound to p articulate and colloidal organic carbon, it is probable that contamina nt entry into cells is directly related to the extracellular and intra cellular behaviour of particulates/colloids with adsorbed chemicals. T he aim of this paper is to consider the cellular mechanisms of accumul ation of organic micropollutants, with emphasis on endocytotic uptake of particulate organic carbon with sorbed contaminant :ligands. In thi s context, lysosomal accumulation of toxic metals and organic xenobiot ics is a well-documented cellular phenomenon, and it has been repeated ly demonstrated that induced lysosomal damage is also a significant fa ctor in cell injury. Sequestration in lysosomes has also been postulat ed to have a protective role through the physical detoxication of poll utants. Physical chemical binding of ligands to lysosomal lipofuscin i s also considered in relation to pollutant storage capacity and thresh olds for cell injury. The role of reactive oxygen species and autophag ic catabolism of proteins is also considered in relation to lipofuscin generation and its protective role. A mathematical model is developed for the intracellular behaviour and toxicity of particulate-bound mic ropollutants that encompasses all of the factors considered above, as well as diffusion of ligand into cells and lysosomes and multidrug-res istance (MDR) mediated transport from the cytosol into endosomes and l ysosomes. Finally, the hypothesis is proposed that lysosomes are pread apted to stress and, secondly,, it is conjectured that animals with hi ghly developed cellular lysosomal systems are more tolerant of polluta nts. Crown Copyright (C) 1998 Elsevier Science Ltd. All rights reserve d.