Abstract
In gills of the marine mussel Mytilus galloprovincialis there is a P-glycoprotein-mediated multixenobiotic resistance mechanism (MXRM) which is similar to the multidrug resistance (MDR) mechanism in tumor cells resistant to cytotoxic drugs. This mechanism in mussel gills could be inhibited by verapamil, a known competitive inhibitor of P-glycoprotein, as measured by the enhanced accumulation of (G- 3H)vincristine (VCR). The activity of MXRM is indicated to be regulated in mussel by protein kinase C (PKC), since the PKC-specific inhibitor, bisindolylmaleimide, inhibits its activity. Similar inhibitory effects were exerted by a water-extract of Diesel-2 oil, or xenobiotics from the XAD-2 concentrates of river water or river sediment pore-water. MXRM was elevated in mussel specimens living at, or transplanted to, a polluted site, as demonstrated by the striking decrease in the rate of VCR accumulation. These results indicate that MXRM may be used as a biomarker of exposure to pollutants, and stress the importance of a new type of hazardous xenobiotic — the ‘chemosensitizers’ of MXRM.
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