Cigarette smoke exposure produces more evidence of emphysema in B6C3F1 mice than in F344 rats

Cigarette smoke (CS) causes pulmonary emphysema in humans, but results of p revious studies on CS-exposed laboratory animals have been equivocal and ha ve not clearly demonstrated progression of the disease, In this study, morp hometry and histopathology were used to assess emphysema in the lungs of B6 C3F1 mice and Fischer-344 rats. The animals were exposed, whole-body, to CS at a concentration of 250 mg total particulate matter/m(3) for 6 h/day, 5 days/week, for either 7 or 13 months. Morphometry included measurements of parenchymal air space enlargement (alveolar septa mean linear intercept [L- m], volume density of alveolar air space [V-Vair]), and tissue loss (volume density of alveolar septa [V-Vspt]). In addition, centriacinar intra-alveo lar inflammatory cells were counted to assess species differences in the ty pe of inflammatory response associated with CS exposure. In mice, many of t he morphometric parameters indicating emphysema differed significantly betw een CS-exposed and control animals. In CS-exposed rats, only some of the pa rameters differed significantly from control values. The L-m in both CS-exp osed mice and rats was increased at 7 and 13 months, indicating an enlargem ent of parenchymal air spaces, but the V-Vair was increased significantly o nly in CS-exposed mice. The V-Vspt was decreased at both time points in mic e, but not in rats, indicating damage to the structural integrity of parenc hyma, Morphologic evidence of tissue destruction in the mice included alveo li that were irregular in size and shape and alveoli with multiple foci of septal discontinuities and isolated septal fragments. Morphometric differen ces in the mice at 13 months were greater than at 7 months, suggesting a pr ogression of the disease. Inflammatory lesions within the lungs of mice con tained significantly more neutrophils than those lesions in rats. These res ults suggest that B6C3F1 mice are more susceptible than F344-rats to the in duction of emphysema by this CS exposure regimen and that in mice the emphy sema may be progressive, Furthermore, the type of inflammatory response may be a determining factor for species differences in susceptibility to emphy sema induction by CS exposure.