INDUCTION AND REVERSION OF MULTIXENOBIOTIC RESISTANCE IN THE MARINE SNAIL MONODONTA-TURBINATA

Many marine organisms inherently express the presence and function of a new defence mechanism, termed multixenobiotic resistance mechanism ( MXRM) because of its similarity to multidrug resistance (MDR) found in tumor cell lines resistant to chemotherapeutic drugs. However, previo usly no information was available on a possible induction of the activ ity of MXRM in organisms living at polluted sites. The purpose of the present study was to demonstrate the inducibility of this defence mech anism in the marine snail Monodonta turbinata, an organism known to in habit a wide range of environmental conditions existing along a pollut ion gradient. Specimens of M. turbinata used in the present study were collected from March 1993 through March 1994 near Rovinj, Croatia. Th e accumulation of generally labelled H-3-vincristine (H-3-VCR) in the gills of snails living at an unpolluted site was 67% higher and very s ensitive to verapamil, an inhibitor of P-glycoprotein activity in comp arison to snails living at a polluted site. The accumulation of vincri stine (VCR) in snails from a polluted site was reduced and insensitive to verapamil due to the induced state of P-glycoprotein, as was demon strated immunochemically by the enhanced concentration of a 140 kDa pr otein cross-reacting with the polyclonal antibodies raised against mam malian P-glycoprotein. MXRM could be induced in snails from the unpoll uted site to the level found in snails living at a polluted site eithe r by transplantation for 3 d to a polluted site, or by exposure for 3 d to sea water polluted will Diesel-2 oil (hydrocarbon concentration e quivalent to 50 ppb of Kuwait oil). Discovery of the inducibility of t his new defence mechanism in aquatic organisms may have important impl ications in ecotoxicology, as was demonstrated by a 104% enhanced accu mulation of VCR in the presence of the MXRM-inhibitor, the so-called ' 'chemosensitizer''. Besides, a striking difference in the levels of MX RM-elements (the sensitivity of the accumulation rate of xenobiotics t o verapamil, immunochemical expression of P-glycoprotein, and the sens itivity of the binding of xenobiotics on membrane vesicles to verapami l) found between specimens living at the polluted and unpolluted sites offers a new molecular biomarker for exposure to pollutants.