EFFECTS OF 0.25 PPM NITROGEN-DIOXIDE ON THE DEVELOPING MOUSE LUNG .1.QUANTITATION OF TYPE-2 CELLS AND MEASUREMENTS OF ALVEOLAR WALLS

Weanling Swiss-Webster male mice were exposed intermittently to 0.25 p pm NO2. Lactate dehydrogenase stained frozen sections of gelatin-infla ted lungs were used for image analysis measurements of Type 2 cells an d alveolar walls at 3 test periods, immediately after 6 wk of exposure , 10 wk postexposure, and 32 wk postexposure, for a total of 196 contr ol and 196 exposed animals. NO2 exposure resulted in a trend toward Ty pe 2 cell hyperplasia and hypertrophy at all 3 test periods, but signi ficant increases in number and size (mean area) of Type 2 cells did no t occur until the 32-wk postexposure test (p = .002 and p <.04, respec tively). Alveolar wall area, perimeters, and linear intercepts were al so consistently greater for the exposed animals at all three test peri ods, with perimeters and intercepts at borderline levels of significan ce at the first test period (p =.09 and p = .08, respectively). An inc rease in the ratio of Type 2 cell number to alveolar wall area (exclud ing Type 2 cells within the walls) for the NO2-exposed animals approac hed significance al the 32-wk postexposure period (p =.08). The delay in the detection of significant cant Type 2 cell alterations until the 32-wk postexposure test seems best explained by an adverse effect of NO2 exposure on lung development and maturation during the 3-9 wk of a ge growth period when exposure took place. Since significant Type 2 ce ll alterations were present 32 wk after exposure (41 wk of age), it se ems likely that injury to Type 1 cells of the alveolar epithelial lini ng (implicated by the Type 2 cell hyperplasia) has occurred and was no t completely reversible. The concomitant occurrence of an increase in Type 2 cell size is in accord with reports of NO2-induced edematous sw elling but may also reflect a functional hypertrophy. The data add to cumulative evidence that an ambient level of NO2 has an adverse effect on the mammalian lung.