title: Responsiveness of hepatic and cerebral cytochrome P450 in rat offspring prenatally and lactationally exposed to a reconstituted PCB mixture.
abstract: Perinatal polychlorinated biphenyl (PCB) exposures still remain a serious health concern because offspring receive PCB burden from mother during vulnerable processes of development. Since cytochrome P450 (CYP) represents a toxicological endpoint, in the present study, representing an extended investigation of a previous multitasked one, we explored the long-term responsiveness of CYP1A and CYP2B isoforms by Western blot analysis in liver and whole brain of lactating (PN12), weaning (PN21), and adult offspring (PN60) rats prenatally and lactationally exposed to a reconstituted PCB mixture (RM) of noncoplanar PCB138, 153, 180, and coplanar PCB126 congeners. We chose highly chlorinated PCBs instead of lower chlorinated one, because their recalcitrance to biotransformation makes easy their accumulation/persistence in tissues and breast milk. Dioxin-like congener PCB126 binding aryl hydrocarbon receptor (AHR) is responsible of many toxic effects. Pregnant Sprague-Dawley dams with high affinity AHR received subcutaneous injection of RM (10 mg/kg body weight) daily during gestation (days 15-19) and twice a week during breast-feeding. The results evidenced a transfer of PCBs to neonates through milk and a significant responsiveness of hepatic CYP in both mothers and offspring. In liver of exposed progeny, CYP isoforms exhibited a significant increment at PN12 (70% over control) and at PN21 (270% over control). Contrary to dams, in adult PCB offspring CYP levels showed a decline up to values similar to those of control. This transient developmental responsiveness of CYP isoforms in offspring liver reflects roughly the time course of hepatic PCB levels previously reported. Even if congeners were detected in brain, we failed in evidencing a responsiveness of CYP isoforms probably because of region-specific CYP expression in this organ. In conclusion, induction of offspring hepatic CYP is index of liver PCB burden, and despite the insensitivity of whole brain CYP we cannot exclude brain vulnerability toward PCB. © 2012 Wiley Periodicals, Inc. Environ Toxicol 29: 856-866, 2014.
authors.affiliation: Dipartimento di Scienze dell'Ambiente e del Territorio, Università di Milano Bicocca, P.zza della Scienza 1, 20126 Milano, Italy.
authors.forename: Patrizia
authors.initials: P
authors.lastname: Bonfanti
authors.forename: Francesca
authors.initials: F
authors.lastname: Comelli
authors.forename: Laura
authors.initials: L
authors.lastname: Assi
authors.forename: Lavinia
authors.initials: L
authors.lastname: Casati
authors.forename: Alessandra
authors.initials: A
authors.lastname: Colciago
authors.forename: Sara
authors.initials: S
authors.lastname: Villa
authors.forename: Angela
authors.initials: A
authors.lastname: Santagostino
authors.forename: Barbara
authors.initials: B
authors.lastname: Costa
authors.forename: Anita
authors.initials: A
authors.lastname: Colombo
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000378:metabolism*; D019363:Cytochrome P-450 CYP1A1 / Q000378:metabolism; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D004785:Environmental Pollutants / Q000378:metabolism / Q000633:toxicity*; D005260:Female; D007527:Isoenzymes / Q000378:metabolism; D007774:Lactation / Q000378:metabolism*; D008099:Liver / Q000378:metabolism*; D008297:Male; D018811:Maternal Exposure; D008892:Milk / Q000378:metabolism; D010084:Oxidation-Reduction; D011078:Polychlorinated Biphenyls / Q000378:metabolism / Q000633:toxicity*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D018336:Receptors, Aryl Hydrocarbon / Q000378:metabolism; D014018:Tissue Distribution
chemical_list: D004785:Environmental Pollutants; D007527:Isoenzymes; D018336:Receptors, Aryl Hydrocarbon; D003577:Cytochrome P-450 Enzyme System; D011078:Polychlorinated Biphenyls; D019363:Cytochrome P-450 CYP1A1