1 expression in specific lung compartments in the developing neonatal and adult rat 2 3

249/250 words) 41 Vehicle exhaust is rich in polycyclic aromatic hydrocarbons (PAH) and can be a dominant 42 contributor to ultrafine urban particulate matter (PM). Exposure to ultrafine PM is correlated with 43 respiratory infections and asthmatic symptoms in young children. The lung undergoes 44 substantial growth, alveolarization and cellular maturation within the first years of life, which may 45 be impacted by environmental pollutants such as PM. PAHs in PM can serve as ligands for the 46 aryl hydrocarbon receptor (AhR) which induces expression of certain isozymes in the 47 cytochrome P450 superfamily, such as CYP1A1 and CYP1B1, localized in specific lung cell 48 types. Although AhR activation and induction has been widely studied, its context within PM 49 exposure and impact on the developing lung is poorly understood. In response, we have 50 developed a replicable ultrafine premixed flame particle (PFP) generating system and used in 51 vitro and in vivo models to define PM effects on AhR activation in the developing lung. We 52 exposed 7-day neonatal and adult rats to a single 6-hour PFP exposure and determined that 53 PFPs cause significant parenchymal toxicity in neonates. PFPs contain weak AhR agonists that 54 upregulate AhR-XRE activity and expression, and are capable inducers of CYP1A1 and 55 CYP1B1 expression in both ages with different spatial and temporal patterns. Neonatal 56 CYP1A1 expression was muted and delayed compared to adults, possibly due to differences in 57 the enzyme maturation. We conclude that the inability of neonates to sufficiently adapt in 58 response to PFP exposure may, in part, explain their susceptibility to PFP and urban ultrafine 59 PM. 60