A New Type of Hazardous Chemical:
The Chemosensitizers of Multixenobiotic Resistance
Branko Kurelec
Center for Marine Research, Ruder Boskovic Institute, Zagreb, Croatia
Abstract
The purpose of this overview is to introduce the property of a new class 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-glycoprotein extrusion pump in multidrug resistant (MDR) tumor cells. MXR in aquatic organism moves from cells and organisms both endogenous chemicals and xenobiotics, including also some man-made chemicals. MXR in aquatic organisms represents a general biological first-line defense mechanism for protection against environmental toxins. Many chemical agents, the chemosensitizers, may alter the function of this fragile mechanism. It is this new, MXR-inhibiting property, unrecognized as yet, that classifies these chemicals among top-rank hazardous water pollutants. The knowledge that the presence of one xenobiotic may block the pumping out of other xenobiotic(s), and hence accelerate their accumulation, may have important implications on environmental parameters like exposure, uptake, bioaccumulation, and toxicity. In this overview we present the evidence for the expression of MXR-phenotype in aquatic organisms, the demonstration of toxic consequences caused by MXR inhibitors, and the description of methods for measurement of concentration of MXR inhibitors in environmental samples. -- Environ Health Perspect 105(Suppl 4):855-860 (1997)
Key words: aquatic organisms, chemosensitizers, determination of, induction, inhibition, multixenobiotic resistance, P170 glycoprotein
This paper was prepared as background for the Workshop on Susceptibility to Environmental Hazards convened by the Scientific Group on Methodologies for the Safety Evaluation of Chemicals (SGOMSEC) held 17-22 March 1996 in Espoo, Finland. Manuscript received at EHP 5 November 1996; accepted 18 November 1996.
This work has been supported by the Ministry for Science of the Republic of Croatia.
Address corespondence to Dr. B. Kurelec, Ruder Boskoviac Institute, Bijenicka 54, 10,000 Zagreb, Croatia. Telephone: 385 1 276483. Fax: 385 1 276483. E-mail: kurelec@olimp.irb.hr
Abbreviations used: MDR, multidrug resistance; MXR, multixenobiotic resistance; P170, membrane 170 kD P-glycoprotein.
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Last Update: June 18, 1997