Inducibility of the P-glycoprotein transport activity in the marine mussel Mytilus galloprovincialis and the freshwater mussel Dreissena polymorpha.
Previous investigations directed to the determination of the P-glycoprotein (Pgp) expression in aquatic organisms have indicated the possibility of the multixenobiotic resistance mechanism (MXR) induction as a response to organic pollution. However, in numerous cases no significant and/or no clear relationship between Pgp contents and pollution level was detected. Concerning these discrepancies the results of an extensive, 3-year study of the Pgp mediated MXR induction in the selected freshwater (Dreissena polymorpha) and marine (Mytilus galloprovincialis) bivalves are presented here. The main goals of the study were to ascertain the rate-dynamic, level, as well as the possible usability of MXR in environmental biomonitoring. Since the primary result of MXR induction should be the decreased intracellular accumulation of xenobiotics, the determination of MXR induction was performed using the measurement of Pgp transport activity. We measured the accumulation or the efflux rate of the model Pgp substrate rhodamine B (RB) in gills of the mussels previously exposed to pollution. The study was performed in several steps: from the exposure experiments in laboratory, using model inducers rhodamine 123 (R123) and water extract of Diesel-2 oil (D2), to the final in situ testing in real environmental conditions. Our results confirmed that Pgp activity is induced/induces according to the level of pollution, and that 4-days period was already long enough for the significant induction and deinduction of MXR activity. However, the inducibility of Pgp transport activity was significantly limited--the maximal level of induction obtained in this study resulted in 50-60% lower RB accumulation in the gills of induced specimens (laboratory or in situ exposed to pollution), when compared to control, non-induced animals. The obtained level of Pgp related MXR induction, resulting in halfway lesser accumulation of a model pollutant (RB), extrapolated to the similar scenario with toxic xenobiotics may have significant environmental relevance. However, our results also suggest that for the use of the MXR as a relevant biomarker the Pgp transport activity should be measured along with the determination of DNA, mRNA or/and protein expression. Based on the data from this study several factors that may have had critical influence on the effectiveness and the level of MXR induction are additionally discussed.
Smital
Tvrtko
T
Department for Marine and Environmental Research, Laboratory for Molecular Ecotoxicology, Rudjer Boskovic Institute, PO Box 180, Bijenicka 54, 10 000 Zagreb, Croatia. smital@rudjer.irb.hr
Sauerborn
Roberta
R
Hackenberger
Branimir K
BK
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000493:pharmacokinetics*; D000704:Analysis of Variance; D000818:Animals; D049872:Bivalvia / Q000378:metabolism*; D017523:Croatia; D005453:Fluorescence; D005618:Fresh Water; D005880:Gills / Q000737:chemistry*; D012235:Rhodamines / Q000737:chemistry*; D012623:Seawater; D014877:Water Pollution, Chemical / Q000032:analysis; D015262:Xenobiotics / Q000378:metabolism
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D012235:Rhodamines; D015262:Xenobiotics; C029773:rhodamine B