title: Increased susceptibility to hyperoxic lung injury and alveolar simplification in newborn rats by prenatal administration of benzo[a]pyrene.
abstract: Maternal smoking is one of the risk factors for preterm birth and for the development of bronchopulmonary dysplasia (BPD). In this study, we tested the hypothesis that prenatal exposure of rats to benzo[a]pyrene (BP), a component of cigarette smoke, will result in increased susceptibility of newborns to oxygen-mediated lung injury and alveolar simplification, and that cytochrome P450 (CYP)1A and 1B1 enzymes and oxidative stress mechanistically contribute to this phenomenon. Timed pregnant Fisher 344 rats were administered BP (25 mg/kg) or the vehicle corn oil (CO) on gestational days 18, 19 and 20, and newborn rats were either maintained in room air or exposed to hyperoxia (85% O2) for 7 or 14 days. Hyperoxic newborn rats prenatally exposed to the vehicle CO showed lung injury and alveolar simplification, and inflammation, and these effects were potentiated in rats that were prenatally exposed to BP. Prenatal exposure to BP, followed by hyperoxia, also resulted in significant modulation of hepatic and pulmonary cytochrome P450 (CYP)1A and 1B1 enzymes at PND 7-14. These rats displayed significant oxidative stress in lungs at postnatal day (PND) 14, as evidenced by increased levels of the F2-isoprostane 8-iso-PGF2α. Furthermore, these animals showed BP-derived DNA adducts and oxidative DNA adducts in the lung. In conclusion, our results show increased susceptibility of newborns to oxygen-mediated lung injury and alveolar simplification following maternal exposure to BP, and our results suggest that modulation of CYP1A/1B1 enzymes, increases in oxidative stress, and BP-DNA adducts contributed to this phenomenon.
authors.affiliation: Department of Pediatrics, Section of Neonatology, Texas Children's Hospital, Baylor College of Medicine, 1102 Bates Avenue, MC: FC530.01, Houston, TX 77030, USA.
authors.forename: Vijay S
authors.initials: VS
authors.lastname: Thakur
authors.affiliation: Department of Pediatrics, Section of Neonatology, Texas Children's Hospital, Baylor College of Medicine, 1102 Bates Avenue, MC: FC530.01, Houston, TX 77030, USA.
authors.forename: Yanhong W
authors.initials: YW
authors.lastname: Liang
authors.affiliation: Department of Pediatrics, Section of Neonatology, Texas Children's Hospital, Baylor College of Medicine, 1102 Bates Avenue, MC: FC530.01, Houston, TX 77030, USA.
authors.forename: Krithika
authors.initials: K
authors.lastname: Lingappan
authors.affiliation: Department of Pediatrics, Section of Neonatology, Texas Children's Hospital, Baylor College of Medicine, 1102 Bates Avenue, MC: FC530.01, Houston, TX 77030, USA.
authors.forename: Weiwu
authors.initials: W
authors.lastname: Jiang
authors.affiliation: Department of Pediatrics, Section of Neonatology, Texas Children's Hospital, Baylor College of Medicine, 1102 Bates Avenue, MC: FC530.01, Houston, TX 77030, USA.
authors.forename: Lihua
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Pathology and Genomic Medicine, The Methodist Hospital Physician Organization, 6565 Fannin Street, Suite M227, Houston, TX 77030, USA.
authors.forename: Roberto
authors.initials: R
authors.lastname: Barrios
authors.affiliation: Institute of Biotechnology, Texas A&M University Health Science Center, Houston, TX 77030, USA.
authors.forename: Guodong
authors.initials: G
authors.lastname: Zhou
authors.affiliation: Department of Pediatrics, Section of Neonatology, Texas Children's Hospital, Baylor College of Medicine, 1102 Bates Avenue, MC: FC530.01, Houston, TX 77030, USA.
authors.forename: Bharath
authors.initials: B
authors.lastname: Guntupalli
authors.affiliation: Department of Pediatrics, Section of Neonatology, Texas Children's Hospital, Baylor College of Medicine, 1102 Bates Avenue, MC: FC530.01, Houston, TX 77030, USA.
authors.forename: Binoy
authors.initials: B
authors.lastname: Shivanna
authors.affiliation: Department of Pediatrics, Section of Neonatology, Texas Children's Hospital, Baylor College of Medicine, 1102 Bates Avenue, MC: FC530.01, Houston, TX 77030, USA.
authors.forename: Paramahamsa
authors.initials: P
authors.lastname: Maturu
authors.affiliation: Department of Pediatrics, Section of Neonatology, Texas Children's Hospital, Baylor College of Medicine, 1102 Bates Avenue, MC: FC530.01, Houston, TX 77030, USA.
authors.forename: Stephen E
authors.initials: SE
authors.lastname: Welty
authors.affiliation: Department of Pediatrics, Section of Neonatology, Texas Children's Hospital, Baylor College of Medicine, 1102 Bates Avenue, MC: FC530.01, Houston, TX 77030, USA.
authors.forename: Bhagavatula
authors.initials: B
authors.lastname: Moorthy
authors.affiliation: Department of Pediatrics, Section of Neonatology, Texas Children's Hospital, Baylor College of Medicine, 1102 Bates Avenue, MC: FC530.01, Houston, TX 77030, USA. Electronic address: xanthic@bcm.edu.
authors.forename: Xanthi I
authors.initials: XI
authors.lastname: Couroucli
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001564:Benzo(a)pyrene / Q000633:toxicity*; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics; D065633:Cytochrome P-450 CYP1B1 / Q000235:genetics; D018736:DNA Adducts / Q000032:analysis; D005260:Female; D005333:Fetus / Q000187:drug effects*; D018496:Hyperoxia / Q000150:complications*; D055370:Lung Injury / Q000209:etiology*; D011247:Pregnancy; D011650:Pulmonary Alveoli / Q000187:drug effects*; D051381:Rats; D011916:Rats, Inbred F344
chemical_list: D018736:DNA Adducts; D001564:Benzo(a)pyrene; D019363:Cytochrome P-450 CYP1A1; D065633:Cytochrome P-450 CYP1B1
keywords: Alveolar simplification; Cytochrome P4501A1/1A2/1B1; Hyperoxic lung injury; Maternal benzo[a]pyrene; Newborn rat; Oxidative stress