title: Subacute nicotine co-exposure has no effect on 2,2',3,5',6- pentachlorobiphenyl disposition but alters hepatic cytochrome P450 expression in the male rat.
abstract: Polychlorinated biphenyls (PCBs) are metabolized by cytochrome P450 2B enzymes (CYP2B) and nicotine is reported to alter CYP2B activity in the brain and liver. To test the hypothesis that nicotine influences PCB disposition, 2,2',3,5',6-pentachlorobiphenyl (PCB 95) and its metabolites were quantified in tissues of adult male Wistar rats exposed to PCB 95 (6mg/kg/d, p.o.) in the absence or presence of nicotine (1.0mg/kg/d of the tartrate salt, s.c.) for 7 consecutive days. PCB 95 was enantioselectively metabolized to hydroxylated (OH-) PCB metabolites, resulting in a pronounced enrichment of E1-PCB 95 in all tissues investigated. OH-PCBs were detected in blood and liver tissue, but were below the detection limit in adipose, brain and muscle tissues. Co-exposure to nicotine did not change PCB 95 disposition. CYP2B1 mRNA and CYP2B protein were not detected in brain tissues but were detected in liver. Co-exposure to nicotine and PCB 95 increased hepatic CYP2B1 mRNA but did not change CYP2B protein levels relative to vehicle control animals. However, hepatic CYP2B protein in animals co-exposed to PCB 95 and nicotine were reduced compared to animals that received only nicotine. Quantification of CYP2B3, CYP3A2 and CYP1A2 mRNA identified significant effects of nicotine and PCB 95 co-exposure on hepatic CYP3A2 and hippocampal CYP1A2 transcripts. Our findings suggest that nicotine co-exposure does not significantly influence PCB 95 disposition in the rat. However, these studies suggest a novel influence of PCB 95 and nicotine co-exposure on hepatic cytochrome P450 (P450) expression that may warrant further attention due to the increasing use of e-cigarettes and related products.
authors.affiliation: Department of Molecular Biosciences, School of Veterinary Medicine, University of California, Davis, California, USA.
authors.forename: Marianna
authors.initials: M
authors.lastname: Stamou
authors.affiliation: Department of Occupational and Environmental Health, College of Public Health, The University of Iowa, Iowa City, Iowa, USA.
authors.forename: Eric
authors.initials: E
authors.lastname: Uwimana
authors.affiliation: Department of Molecular Biosciences, School of Veterinary Medicine, University of California, Davis, California, USA.
authors.forename: Brenna M
authors.initials: BM
authors.lastname: Flannery
authors.affiliation: Department of Occupational and Environmental Health, College of Public Health, The University of Iowa, Iowa City, Iowa, USA.
authors.forename: Izabela
authors.initials: I
authors.lastname: Kania-Korwel
authors.affiliation: Department of Occupational and Environmental Health, College of Public Health, The University of Iowa, Iowa City, Iowa, USA.
authors.forename: Hans-Joachim
authors.initials: HJ
authors.lastname: Lehmler
authors.affiliation: Department of Molecular Biosciences, School of Veterinary Medicine, University of California, Davis, California, USA.
authors.forename: Pamela J
authors.initials: PJ
authors.lastname: Lein
mesh_terms: D000818:Animals; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics / Q000378:metabolism; D001711:Biotransformation; D001921:Brain / Q000187:drug effects / Q000201:enzymology; D019388:Cytochrome P-450 CYP1A2; D019362:Cytochrome P-450 CYP2B1 / Q000235:genetics / Q000378:metabolism; D051544:Cytochrome P-450 CYP3A / Q000235:genetics / Q000378:metabolism; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics / Q000378:metabolism*; D000072467:Cytochrome P450 Family 2; D003580:Cytochromes / Q000235:genetics / Q000378:metabolism; D015971:Gene Expression Regulation, Enzymologic; D006900:Hydroxylation; D008099:Liver / Q000187:drug effects* / Q000201:enzymology; D008297:Male; D009538:Nicotine / Q000008:administration & dosage*; D011078:Polychlorinated Biphenyls / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D017208:Rats, Wistar; D013379:Substrate Specificity; D013997:Time Factors
chemical_list: D003580:Cytochromes; D012333:RNA, Messenger; C032904:2,2',3,5',6-pentachlorobiphenyl; D009538:Nicotine; D003577:Cytochrome P-450 Enzyme System; D011078:Polychlorinated Biphenyls; D001189:Aryl Hydrocarbon Hydroxylases; C017170:Cyp1a2 protein, rat; C089142:Cyp2b3 protein, rat; C465260:Cyp3a2 protein, rat; D019388:Cytochrome P-450 CYP1A2; D019362:Cytochrome P-450 CYP2B1; D051544:Cytochrome P-450 CYP3A; D000072467:Cytochrome P450 Family 2
keywords: Atropselective; CYP1A2; CYP2B1; CYP2B3; CYP3A2; Cytochrome P450 enzymes; Disposition; Nicotine; Polychlorinated biphenyls; Wistar rat