A NEW-TYPE OF HAZARDOUS CHEMICAL - THE CHEMOSENSITIZERS OF MULTIXENOBIOTIC RESISTANCE

The purpose of this overview is to introduce the property of a new cla ss of hazardous chemicals-the inhibitors of multixenobiotic resistance (MXR) in aquatic organisms, referred to;as chemosensitizers. Aquatic organisms possess MXR, a mechanism similar to the well-known P-glycopr otein extrusion pump in multidrug resistant (MDR) tumor cells. MXR in aquatic organism moves from cells and organisms both endogenous chemic als and xenobiotics, including also some man-made chemicals. MXR in aq uatic organisms represents a general biological first-line defense mec hanism for protection against environmental toxins. Many chemical agen ts, the chemosensitizers. may alter the function of this fragile mecha nism. It is this new, MXR-inhibiting property, unrecognized as yet, th at classifies these chemicals among top-rank hazardous water pollutant s. The knowledge that the presence of one xenobiotic may block the pum ping out of other xenobiotic(s). and hence accelerate their accumulati on, may have important implications on environmental parameters like e xposure, uptake, bioaccumulation, and toxicity. In this overview we pr esent the evidence for the expression of MXR-phenotype in aquatic orga nisms, the demonstration of toxic consequences caused by MXR inhibitor s, and the description of methods for measurement of concentration of MXR inhibitors in environmental samples. - Environ Health Perspect 105 (Suppl 4):855-860 (1997).