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 (25mg/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.