THE CHEMOSENSITIZERS OF MULTIXENOBIOTIC RESISTANCE MECHANISM IN AQUATIC INVERTEBRATES - A NEW CLASS OF POLLUTANTS

Mechanism of multixenobiotic resistance (MXR), identical to multidrug resistance (MDR) in tumor-cells, has been found in aquatic invertebrat es. The presence of this ATP-dependent membrane P-glycoprotein (Pgp) p ump was confirmed by biochemical ('binding'), molecular (immunohistoch emical, Western, Northern), physiological (verapamil-sensitivity) and toxicological (modulation of toxicity) methods. The inducibility of MX R in the presence of xenobiotics and its wide taxonomic distribution s uggests its role as a general biological defense mechanism that rescue s organisms by pumping potentially toxic xenobiotics out of the cells. Some xenobiotics, the chemosensitizers, can inhibit this defense mech anism. The presence of these MXR-inhibitors has important implications on environmental parameters like exposure, uptake, internal dose, bio accumulation, response, synergism and toxicity. Such MXR-inhibitors, f or example, enhance the accumulation of carcinogenic aromatic amines i n mussel, with subsequent enhancement in production of their mutagenic metabolites, in induction of single strand breaks in DNA, and in indu ction of DNA-adducts. The property to inhibit defense mechanism of org anisms classifies MXR-inhibitors among top-hazardous environmental che micals. Therefore, we measured the concentration of chemosensitizers i n water concentrates or sediment extracts as their potential to modula te the accumulation of fluorescent dyes in a cell-culture of NIH 3T3 m ouse fibroblasts stable transfected with human MDR1 gene, or as the po tential of native waters to decrease the efflux-rate of Rhodamine B fr om gills of mussels. We found significantly higher concentrations of M XR-inhibitors in samples from polluted marine sites or from polluted r ivers than in samples from corresponding unpolluted sites. These conce ntrations were able to enhance the accumulation of fluorescent dyes or carcinogenic aromatic amines in clams, mussels, snails and sponges ex posed to these xenobiotics, demonstrating the ecotoxicological relevan ce of MXR-inhibitors present in polluted waters. (C) 1998 Elsevier Sci ence B.V.