A model for cellular uptake and intracellular behaviour of particulate-bound micropollutants

The uptake and subsequent behaviour and toxicity of organic micropollutants in organisms is governed by the physical chemical speciation of these contaminants. Since lipophilic pollutants are largely bound to particulate and colloidal organic carbon, it is probable that contaminant entry into cells is directly related to the extracellular and intracellular behaviour of particulates/colloids with adsorbed chemicals. The aim of this paper is to consider the cellular mechanisms of accumulation of organic micropollutants, with emphasis on endocytotic uptake of particulate organic carbon with sorbed contaminant ligands. In this context, lysosomal accumulation of toxic metals and organic xenobiotics is a well-documented cellular phenomenon, and it has been repeatedly demonstrated that induced lysosomal damage is also a significant factor in cell injury. Sequestration in lysosomes has also been postulated to have a protective role through the physical detoxication of pollutants. Physical chemical binding of ligands to lysosomal lipofuscin is also considered in relation to pollutant storage capacity and thresholds for cell injury. The role of reactive oxygen species and autophagic 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 micropollutants that encompasses all of the factors considered above, as well as diffusion of ligand into cells and lysosomes and multidrug-resistance (MDR) mediated transport from the cytosol into endosomes and lysosomes. Finally, the hypothesis is proposed that lysosomes are preadapted to stress and, secondly, it is conjectured that animals with highly developed cellular lysosomal systems are more tolerant of pollutants.