Recent studies from our laboratory have demonstrated that rats are highly sensitive to ozone-induced pulmonary inflammation during late pregnancy and throughout lactation compared to both age-matched virgin female and postlactating rats. The greater response of lactating rats compared to virgin females is characterized by a striking 300% enhancement of both lavage protein concentration and lavaged polymorphonuclear leukocytes after a single 6 hour exposure to 0.5 ppm ozone. The major focus of this project is an investigation of the mechanism(s) underlying the sensitivity or predisposition to ozone of rats in states of advanced, pregnancy and lactation. Three areas of documented or potential physiological/biochemical change during pregnancy and lactation will be investigated.These are: 1) ventilation, 2) fatty acid composition of membrane phospholipids, and 3) oxidant/antioxidant balance. Parameters of ventilation will be measured in ozone-sensitive (lactating/pregnant) and ozone-insensitive (postlactating/prepregnant) rats before and during exposure to ozone in a barometric plethysmograph. The relationship between pulmonary damage and ventilatory parameters will be established to determine the extent to which altered ventilation might account for the difference in responsiveness to atmospheric ozone. In addition, regional dosimetry to lung tissues of ozone-sensitive and insensitive rats will be estimated from 18-oxygen binding following exposure to 18-oxygen labeled ozone. These data will be used to assess the importance of dose i explaining the greater sensitivity or responsiveness of pregnant and lactating rats to ozone. The ratio of unsaturated to saturated fatty acids in membrane phospholipids is an important determinant of membrane, properties and function, and also affects the number of potential ozone- reactive sites. Putative changes in phospholipid fatty acid composition that occur during pregnancy and lactation will be investigated as well as the modulation of these changes and ozone toxicity by dietary intake of polyunsaturated fatty acids. Numerous antioxidants oppose the action of ozone and its toxic metabolites. The composition of the antioxidant milieu in the lungs during pregnancy and lactation will be compared to that of ozone-insensitive stages. Changes in antioxidant activity in response to ozone exposure will be explored to identify those antioxidants of greatest functional importance. An additional aim of this project is to describe the location and severity of histological changes in ozone-sensitive (lactating) and ozone-insensitive (virgin or post lactating) rats following single or repeated exposures to ozone. Damage to the trachea, bronchi, bronchioles and centriacinar regions of the lung will be assessed quantitatively.
| Gunnison, A F; Hatch, G E (1999) O3-induced inflammation in prepregnant, pregnant, and lactating rats correlates with O3 dose estimated by 18O. Am J Physiol 276:L332-40 |
| Gunnison, A F; Finkelstein, I (1997) Rat lung phospholipid fatty acid composition in prepregnant, pregnant, and lactating rats: relationship to ozone-induced pulmonary toxicity. Lung 175:127-37 |
| Gunnison, A F; Bowers, A; Nadziejko, C et al. (1997) Modulation of the inflammatory effects of inhaled ozone in rats by subcutaneous prolactin-secreting, pituitary-derived tumors. Fundam Appl Toxicol 37:88-94 |
