Prenatal exposure to polycyclic aromatic hydrocarbons (PAHs) augments neonatal hyperoxic lung injury: Role of cytochrome P450 (CYP)1A1, 1A2, and 1B1

• Published in: Free radical biology & medicine 2024-02, Vol.211, p.35-46
• Main Authors: Stading, Rachel, Swanson, Lauren, Xia, Guobin, Jiang, Weiwu, Wang, Lihua, Couroucli, Xanthi, Lingappan, Krithika, Moorthy, Bhagavatula
• Format: Article
• Language: English
• Subjects: Alveolar simplification; Animals; Cytochrome P-450 CYP1A1 - genetics; Cytochrome P-450 CYP1A1 - metabolism; Cytochrome P-450 CYP1A2 - genetics; Cytochrome P-450 CYP1A2 - metabolism; Cytochrome P-450 Enzyme System; Cytochrome P450 1A1/1A2/1B1; Female; Humans; Hyperoxia; Hyperoxia - complications; Hyperoxia - genetics; Infant, Newborn; Lung - metabolism; Lung Injury - chemically induced; Mice; Mice, Inbred C57BL; Mice, Knockout; Newborn lung injury; Oxidative stress; Oxygen; Polycyclic aromatic hydrocarbon; Polycyclic Aromatic Hydrocarbons - metabolism; Polycyclic Aromatic Hydrocarbons - toxicity; Pregnancy; Prenatal Exposure Delayed Effects
• ISSN: 0891-5849; 1873-4596
• DOI: 10.1016/j.freeradbiomed.2023.12.001

Pregnant women exposed to polycyclic aromatic hydrocarbons (PAHs) are at increased risk for premature delivery. Premature infants often require supplemental oxygen, a known risk factor for bronchopulmonary dysplasia (BPD). Cytochrome P450 (CYP) enzymes have been implicated in hyperoxic lung injury. We hypothesize that prenatal PAH exposure exacerbates oxygen-mediated lung injury in neonatal mice, and that this effect is differentially altered in mice lacking the gene for (Cyp)1a1, 1a2, or 1b1. Timed pregnant wild type (WT) (C57BL/6J) mice were orally administered a PAH mixture of benzo[a]pyrene (BP) and benzo[b]fluoranthene (BbF) or the vehicle corn oil (CO) once daily on gestational days 16–19, and the dose response on postnatal lung injury was examined. In addition, timed pregnant mice with one of four genotypes, WT, Cyp1a1-null, Cyp1a2-null, and Cyp1b1-null, were treated orally with CO or PAH on gestational days 16–19 and exposed to hyperoxia or room air for 14 days. Lung injury was assessed on PND15 by radial alveolar count (RAC) and mean linear intercept (MLI) Gene expression of DNA repair genes in lung and liver were measured. Results showed that neonatal hyperoxic lung injury is augmented by prenatal PAH exposure in a dose-dependent manner. This effect was differentially altered in the Cyp-null mice, with Cyp1a2-null showing the greatest extent of lung injury. We concluded that newborn mice exposed to PAH in utero had more significant lung injury in response to hyperoxia than non-PAH exposed pups, and that CYP1A1 and CYP1A2 are protective against lung injury while CYP1B1 augments lung injury. [Display omitted] •Hyperoxic lung injury is augmented by prenatal polycyclic hydrocarbon (PAH) exposure in a dose-dependent manner.•Hyperoxic lung injury is differentially altered in Cyp1a1-null, Cyp1a2-null and Cyp1b1-null mice.•Angiogenesis is significantly decreased under PAH and hyperoxic conditions.•Prenatal PAH exposure causes induction of Cyp1a1 and 1b1 under hyperoxia.•Prenatal PAH exposure and postnatal hyperoxia cause induction of pulmonary DNA repair genes.