O3-induced inflammation in prepregnant, pregnant, and lactating rats correlates with O3 dose estimated by 18O

1 Nelson Institute of Environmental Medicine, New York University Medical Center, New York, New York 10016; and 2 Pulmonary Toxicology Branch, Experimental Toxicology Division, United States Environmental Protection Agency, Research Triangle Park, North Carolina 27711 Previous studies have shown that rats late in pregnancy and throughout lactation are more susceptible to ozone (O 3 )-induced pulmonary inflammation than are prepregnant (virgin) or postlactating rats. The major aim of the present study was to determine whether these differences in response intensity could be accounted for by the O 3 dose to the lower region of the lung. The relative O 3 dose to the lower lung of groups of pregnant, lactating, and virgin female rats was estimated by measuring the incorporation of the 18 O isotope into low-speed (cells) and high-speed (surfactant) pellets of bronchoalveolar lavage fluid immediately after acute exposure to 0.5-1.1 parts/million 18 O 3 . The polymorphonuclear leukocyte (PMN) and protein inflammatory responses were established 20 h after acute exposure of identical physiological groups to 0.5-1.1 parts/million 16 O 3 (common isotope). A single regression of PMN inflammation data against surfactant 18 O concentration for all physiological groups gave a linear relationship, indicating direct proportionality of PMN inflammation with this estimate of relative dose to the lower lung regardless of physiological status. This implies that the chemical species that react with surfactant molecules, i.e., O 3 or its metabolites, are the same as or proportional to those chemical species responsible for initiating PMN inflammation. Additional experiments showed that lung tissue ascorbic acid concentration was significantly lower in pregnant and lactating rats than in virgin female rats. Although a causative relationship cannot be assumed, the deficit in tissue ascorbic acid concentration in pregnant and lactating rats compared with virgin female rats is consistent with their greater responsiveness and higher relative surfactant O 3 dose. ozone; ascorbic acid; antioxidant; surfactant; polymorphonuclear leukocyte