title: Gestational and lactational exposure to the polychlorinated biphenyl mixture Aroclor 1254 modulates retinoid homeostasis in rat offspring.
abstract: Polychlorinated biphenyls (PCBs) induce a broad spectrum of biochemical and toxic effects in mammals including alterations of the vital retinoid (vitamin A) system. The aim of this study was to characterize alterations of tissue retinoid levels in rat offspring and their dams following gestational and lactational exposure to the PCB mixture Aroclor 1254 (A1254) and to assess the interrelationship of these changes with other established sensitive biochemical and toxicological endpoints. Sprague-Dawley rat dams were exposed orally to 0 or 15 mg/kg body weight/day of A1254 from gestational day 1 to postnatal day (PND) 23. Livers, kidneys and serum were collected from the offspring on PNDs 35, 77 and 350. Tissue and serum retinoid levels, hepatic cytochrome P450 (CYP) enzymes and serum thyroid hormones were analyzed. A multivariate regression between A1254 treatment, hepatic retinoid levels, hepatic CYP enzymes activities, thyroid hormone levels and body/liver weights was performed using an orthogonal partial least-squares (PLS) analysis. The contribution of dioxin-like (DL) components of A1254 to the observed effects was also estimated using the toxic equivalency (TEQ) concept. In both male and female offspring short-term alterations in tissue retinoid levels occurred at PND35, i.e. decreased levels of hepatic retinol and retinoic acid (RA) metabolite 9-cis-4-oxo-13,14-dihydro-RA with concurrent increases in hepatic and renal all-trans-RA levels. Long-term changes consisted of decreased hepatic retinyl palmitate and increased renal retinol levels that were apparent until PND350. Retinoid system alterations were associated with altered CYP enzyme activities and serum thyroid hormone levels as well as body and liver weights in both offspring and dams. The estimated DL activity was within an order of magnitude of the theoretical TEQ for different endpoints, indicating significant involvement of DL congeners in the observed effects. This study shows that tissue retinoid levels are affected both short- and long-term by developmental A1254 exposure and are associated with alterations of other established endpoints of toxicological concern.
authors.affiliation: Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden; Instituto de Bioingeniería, Universidad Miguel Hernández de Elche, Elche (Alicante), Spain.
authors.forename: Javier
authors.initials: J
authors.lastname: Esteban
authors.affiliation: Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Lubna E
authors.initials: LE
authors.lastname: Elabbas
authors.affiliation: Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Daniel
authors.initials: D
authors.lastname: Borg
authors.affiliation: Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Maria
authors.initials: M
authors.lastname: Herlin
authors.affiliation: Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Agneta
authors.initials: A
authors.lastname: Åkesson
authors.affiliation: Centro de Investigación Operativa, Universidad Miguel Hernández, Elche (Alicante), Spain.
authors.forename: Xavier
authors.initials: X
authors.lastname: Barber
authors.affiliation: Institute for Food Toxicology and Analytical Chemistry, University of Veterinary Medicine, Hannover, Germany.
authors.forename: Gerd
authors.initials: G
authors.lastname: Hamscher
authors.affiliation: Institute for Food Toxicology and Analytical Chemistry, University of Veterinary Medicine, Hannover, Germany.
authors.forename: Heinz
authors.initials: H
authors.lastname: Nau
authors.affiliation: Neurotoxicology Laboratory, Environmental Health Sciences and Research Bureau, Health Canada, Ottawa, Canada; Neuroscience Department, Carleton University, Ottawa, Canada.
authors.forename: Wayne J
authors.initials: WJ
authors.lastname: Bowers
authors.affiliation: Neurotoxicology Laboratory, Environmental Health Sciences and Research Bureau, Health Canada, Ottawa, Canada.
authors.forename: Jamie S
authors.initials: JS
authors.lastname: Nakai
authors.affiliation: Department of Environmental Health, THL - National Institute for Health and Welfare, Kuopio, Finland; Department of Environmental Science, University of Eastern Finland, Kuopio, Finland.
authors.forename: Matti
authors.initials: M
authors.lastname: Viluksela
authors.affiliation: Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden. Electronic address: Helen.Hakansson@ki.se.
authors.forename: Helen
authors.initials: H
authors.lastname: Håkansson
mesh_terms: D000465:Algorithms; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D020111:Chlorodiphenyl (54% Chlorine) / Q000633:toxicity*; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D023381:Endpoint Determination; D004785:Environmental Pollutants / Q000633:toxicity*; D005260:Female; D006706:Homeostasis / Q000187:drug effects; D007668:Kidney / Q000378:metabolism; D007774:Lactation / Q000502:physiology*; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D006899:Mixed Function Oxygenases / Q000378:metabolism; D009929:Organ Size / Q000187:drug effects; D000072317:Polychlorinated Dibenzodioxins / Q000633:toxicity; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D012176:Retinoids / Q000097:blood / Q000378:metabolism*; D013963:Thyroid Hormones / Q000378:metabolism; D014801:Vitamin A / Q000378:metabolism
chemical_list: D004785:Environmental Pollutants; D000072317:Polychlorinated Dibenzodioxins; D012176:Retinoids; D013963:Thyroid Hormones; D020111:Chlorodiphenyl (54% Chlorine); D014801:Vitamin A; D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases
keywords: Aroclor 1254; Partial least square regression; Perinatal exposure; Polychlorinated biphenyls (PCBs); Retinoids; Toxic equivalency