CHARACTERIZATION OF MULTIXENOBIOTIC MULTIDRUG TRANSPORT IN THE GILLS OF THE MUSSEL MYTILUS-CALIFORNIANUS AND IDENTIFICATION OF ENVIRONMENTAL SUBSTRATES

Most studies on resistance of organisms to xenobiotics have focused on mechanisms which metaboIize the compound to some other hopefully nontoxic derivative. Another defense mechanism has recently been described in which a multixenobiotic transport protein exports moderately hydrophobic compounds from the cells, thus reducing their accumulation in the cells. In this study we describe a simple fluorescent dye assay to measure multixenobiotic transport activity in the gills of the mussel Mytilus californiamus. The assay is also used to identify potential substrates os inhibitors of the transport mechanism by their ability to inhibit dye transport from the cells (resulting in their increased fluorescence). Several moderately hydrophobic pesticides including DCPA or dacthal, chlorbenside, pentachlorophenol, and CDEC or sulfallate do inhibit dye efflux from gill cells indicating that they are substrates or inhibitors, but the more hydrophobic xenobiotics DDT, DDD, DDE, and Arclor 1254 do not, indicating that they are not substrates. We also confirm by direct chemical analysis that DCPA is exported from the cell by the multixenobiotic defense mechanism; DCPA levels in mussel gills are enhanced when an inhibitor of the transporter is present. M. californianus gills also have a protein of 170 kDa that is immunologically related to the mammalian multidrug transport protein (responsible for multidrug resistance, a phenomenon similar to the multixenobiotic defense mechanism). M. californianus and other marine organisms may use multixenobiotic transport to reduce the accumulation of potentially harmful environmental xenobiotics in their cells. The implications of these results for biomonitoring studies, such as the Mussel Watch Program, are discussed.