title: Transplacental carcinogenesis with dibenzo[def,p]chrysene (DBC): timing of maternal exposures determines target tissue response in offspring.
abstract: Dibenzo[def,p]chrysene (DBC) is a transplacental carcinogen in mice (15mg/kg; gestation day (GD) 17). To mimic residual exposure throughout pregnancy, dams received four smaller doses of DBC (3.75mg/kg) on GD 5, 9, 13 and 17. This regimen alleviated the previously established carcinogenic responses in the thymus, lung, and liver. However, there was a marked increase in ovarian tumors (females) and hyperplastic testes (males). [(14)C]-DBC (GD 17) dosing revealed transplacental distribution to fetal tissues at 10-fold lower concentrations than in paired maternal tissue and residual [(14)C] 3weeks post-dose. This study highlights the importance of developmental stage in susceptibility to environmental carcinogens.
authors.affiliation: Department of Environmental and Molecular Toxicology, Oregon State University, Corvallis, OR 97331, USA.
authors.forename: Lyndsey E
authors.initials: LE
authors.lastname: Shorey
authors.forename: David J
authors.initials: DJ
authors.lastname: Castro
authors.forename: William M
authors.initials: WM
authors.lastname: Baird
authors.forename: Lisbeth K
authors.initials: LK
authors.lastname: Siddens
authors.forename: Christiane V
authors.initials: CV
authors.lastname: Löhr
authors.forename: Melissa M
authors.initials: MM
authors.lastname: Matzke
authors.forename: Katrina M
authors.initials: KM
authors.lastname: Waters
authors.forename: Richard A
authors.initials: RA
authors.lastname: Corley
authors.forename: David E
authors.initials: DE
authors.lastname: Williams
mesh_terms: D000818:Animals; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics / Q000378:metabolism; D001580:Benzopyrenes / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000633:toxicity*; D002273:Carcinogens / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000633:toxicity*; D065633:Cytochrome P-450 CYP1B1; D005260:Female; D005333:Fetus / Q000187:drug effects / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D015971:Gene Expression Regulation, Enzymologic; D005865:Gestational Age; D008297:Male; D018811:Maternal Exposure; D008431:Maternal-Fetal Exchange; D051379:Mice; D057507:Mice, 129 Strain; D009374:Neoplasms, Experimental / Q000139:chemically induced* / Q000473:pathology; D021041:Placental Circulation; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D013997:Time Factors; D014018:Tissue Distribution
chemical_list: D001580:Benzopyrenes; D002273:Carcinogens; D001189:Aryl Hydrocarbon Hydroxylases; C585498:Cyp1b1 protein, mouse; D065633:Cytochrome P-450 CYP1B1; C041517:dibenzo(a,l)pyrene
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