Naslov
The chemosenzitizers of multixenobiotic resistance mechanism in aquatic invertebrates : a new class of pollutants

Autori
Smital, Tvrtko ; Kurelec, Branko

Izvornik
Mutation research (1386-1964) 399 (1998), 1; 43-53

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, ostalo

Ključne riječi
multixenobiotic resistance; aquatic invertebrates; chemosensitizers; determination of; concentrations of; carcinogens; ecotoxicology

Sažetak
Mechanism of multixenobiotic resistance (MXR), identical to multidrug resistance (MDR) in tumor cells, has been found in aquatic invertebrates. The presence of this ATP-dependent membrane P-glycoprotein (Pgp) pump was confirmed by biochemical ("binding"), molecular (immunohistochemical, Western, Northern), physiological (verapamil-sensitivity) and toxicological (modulation of toxicity) methods. The inducibility of MXR in the presence of xenobiotics and its wide taxonomic distribution suggests its role as a general biological defence mechanism that rescues organisms by pumping potentially toxic xenobiotics out of the cells. Some xenobiotics, the chemosensitizers, can inhibit this defence mechanism. The presence of these MXR-inhibitors has important implications on environmental parameters like exposure, uptake, internal dose, bioaccumulation, response, synergism and toxicity. Such MXR-inhibitors, for example, enhance the accumulation of carcinogenic aromatic amines in mussel, with subsequent enhancement in production of their mutagenic metabolites, in induction of single strand breaks in DNA, and in induction of DNA-adducts. The property to inhibit defence mechanism of organisms classifies MXR-inhibitors among top-hazardous environmental chemicals. Therefore we measured the concentration of chemosensitizers in water concentrates or sediment extracts as their potential to modulate the accumulation of fluorescent dyes in a cell-culture of NIH 3T3 mouse fibroblasts stable transfected with human MDR1 gene, or as the potential of native waters to decrease the efflux-rate of Rhodamine B from gills of mussels. We found significantly higher concentrations of MXR-inhibitors in samples from polluted marine sites or from polluted rivers than in samples from corresponding unpolluted sites. These concentrations were able to enhance the accumulation of fluorescent dyes, or carcinogenic aromatic amines, in clams, mussels, snail and sponges exposed to these xenobiotics, demonstrating the ecotoxicological relevance of MXR-inhibitors present in polluted waters.

Izvorni jezik
Engleski

Znanstvena područja
Kemija

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