title: Developmental toxicity of hexachloronaphthalene in Wistar rats. A role of CYP1A1 expression.
abstract: Hexachloronaphthalene (HxCN) is one of the most toxic congeners of polychlorinated naphthalenes (PCNs). This study assesses the prenatal toxicity of HxCN after daily administration at doses of 0.1-1.0mg/kg b.w. to pregnant Wistar rats during organogenesis. We evaluated also the expression of CYP1A1 mRNA and protein in the livers of dams and fetuses, as well as the placenta. The results indicate that 0.3mg/kg b.w. was the lowest HxCN toxic dose for dams (LOAEL) while a dose of 0.1mg/kg b.w. was sufficient to impair the intrauterine development of embryos/fetuses without maternal toxicity. Regardless of the applied dose, HxCN generated embryotoxic effects. Dose-dependent fetotoxic effects were associated with HxCN exposure. HxCN was found to be a strong inducer of maternal and fetal CYP1A1. Expression of CYP1A1 mRNA in the placenta appears to be the most sensitive marker of HxCN exposure.
authors.affiliation: Department of Toxicology, Faculty of Pharmacy, Medical University of Lodz, Poland. Electronic address: anna.kilanowicz@umed.lodz.pl.
authors.forename: Anna
authors.initials: A
authors.lastname: Kilanowicz
authors.affiliation: Department of Cytophysiology, Chair of Histology and Embryology, School of Medicine in Katowice, Medical University of Silesia, Katowice, Poland.
authors.forename: Piotr
authors.initials: P
authors.lastname: Czekaj
authors.affiliation: Department of Toxicology, Faculty of Pharmacy, Medical University of Lodz, Poland.
authors.forename: Andrzej
authors.initials: A
authors.lastname: Sapota
authors.affiliation: Department of Toxicology, Faculty of Pharmacy, Medical University of Lodz, Poland.
authors.forename: Malgorzata
authors.initials: M
authors.lastname: Skrzypinska-Gawrysiak
authors.affiliation: Department of Toxicology, Faculty of Pharmacy, Medical University of Lodz, Poland.
authors.forename: Elzbieta
authors.initials: E
authors.lastname: Bruchajzer
authors.affiliation: Department of Toxicology, Faculty of Pharmacy, Medical University of Lodz, Poland.
authors.forename: Adam
authors.initials: A
authors.lastname: Darago
authors.affiliation: Department of Histology, Chair of Histology and Embryology, School of Medicine in Katowice, Medical University of Silesia, Katowice, Poland.
authors.forename: Ewa
authors.initials: E
authors.lastname: Czech
authors.affiliation: Department of Cytophysiology, Chair of Histology and Embryology, School of Medicine in Katowice, Medical University of Silesia, Katowice, Poland.
authors.forename: Danuta
authors.initials: D
authors.lastname: Plewka
authors.affiliation: Department of Histology, Chair of Histology and Embryology, School of Medicine in Katowice, Medical University of Silesia, Katowice, Poland.
authors.forename: Anna
authors.initials: A
authors.lastname: Wiaderkiewicz
authors.affiliation: Department of Toxicology and Carcinogenesis, Nofer Institute of Occupational Medicine, Lodz, Poland.
authors.forename: Krystyna
authors.initials: K
authors.lastname: Sitarek
mesh_terms: D000818:Animals; D019363:Cytochrome P-450 CYP1A1 / Q000096:biosynthesis* / Q000235:genetics; D065693:Cytochrome P-450 Enzyme Inducers / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D004790:Enzyme Induction; D005260:Female; D005333:Fetus / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D005865:Gestational Age; D008099:Liver / Q000187:drug effects* / Q000196:embryology / Q000201:enzymology; D008297:Male; D009281:Naphthalenes / Q000633:toxicity*; D038081:Organogenesis / Q000187:drug effects; D010920:Placenta / Q000187:drug effects* / Q000201:enzymology; D011247:Pregnancy; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D017208:Rats, Wistar; D018570:Risk Assessment
chemical_list: D065693:Cytochrome P-450 Enzyme Inducers; D009281:Naphthalenes; D012333:RNA, Messenger; C049022:1,2,3,4,5,6-hexachloronaphthalene; D019363:Cytochrome P-450 CYP1A1
keywords: CYP1A1; Developmental toxicity; Embryotoxicity; Placenta; Polychlorinated naphthalenes; Rat