The effects of accumulation of an environmentally relevant polychlorinated biphenyl mixture on cytochrome P450 and P-glycoprotein expressions in fetuses and pregnant rats.
The aim of this study was to improve knowledge about transplacental transfer of an environmentally relevant PCB mixture by evaluating congener levels in livers and brains of rat dams and fetuses after maternal exposure, and correlating them to the levels of CYP450 and P-glycoprotein, involved in biotransformation and xenobiotics export, respectively. Pregnant dams were injected daily from gestation day (GD) 15 to 19 with 10mgkg(-1) of a reconstituted mixture (RM) composed of PCB138, 153, 180 and 126. Our data indicate that at GD20 RM is partitioned among maternal tissues, and that fetuses are not excluded from this distribution, evidencing a placental transfer of PCBs. Considering the ratio of maternal and fetal PCB concentrations based on lipid-weight, the amounts of congeners were 7-fold lower in fetal livers than in maternal livers and 25-30-fold higher in fetal brains than in maternal ones. Moreover, in dams the congeners were able to induce hepatic CYP450 response (total CYP450, CYP1A and CYP2B), but failed to increase P-170 expression, while in fetuses the constitutive expression of CYP450 and P-170 was not induced by treatment. Pearson Product-Moment Correlation applied to treated group data suggests that PCB accumulation in fetal livers, but not in brains, depended principally on their mothers' intoxication pattern. On the whole, these results emphasize the maternal liver and the fetal brain as depot organs for PCB sequestration and their susceptibility towards PCB toxicological risk. Moreover they highlight the lack of a coordinated response between the investigated defence mechanism.
Bonfanti
Patrizia
P
Department of Environmental Sciences, University of Milano-Bicocca, Piazza della Scienza 1, 20126 Milan, Italy. Electronic address: patrizia.bonfanti@unimib.it.
Colombo
Anita
A
Department of Environmental Sciences, University of Milano-Bicocca, Piazza della Scienza 1, 20126 Milan, Italy.
Villa
Sara
S
Department of Environmental Sciences, University of Milano-Bicocca, Piazza della Scienza 1, 20126 Milan, Italy.
Comelli
Francesca
F
Department of Biotechnology and Bioscience, University of Milano-Bicocca, Piazza della Scienza 2, 20126 Milan, Italy.
Costa
Barbara
B
Department of Biotechnology and Bioscience, University of Milano-Bicocca, Piazza della Scienza 2, 20126 Milan, Italy.
Santagostino
Angela
A
Department of Environmental Sciences, University of Milano-Bicocca, Piazza della Scienza 1, 20126 Milan, Italy.
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism*; D000818:Animals; D001711:Biotransformation; D001921:Brain / Q000378:metabolism; D001923:Brain Chemistry; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D004785:Environmental Pollutants / Q000378:metabolism*; D005260:Female; D005333:Fetus / Q000378:metabolism*; D008099:Liver / Q000737:chemistry / Q000378:metabolism; D011078:Polychlorinated Biphenyls / Q000032:analysis*; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D015262:Xenobiotics / Q000032:analysis
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D004785:Environmental Pollutants; D015262:Xenobiotics; D003577:Cytochrome P-450 Enzyme System; D011078:Polychlorinated Biphenyls