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 previous studies on CS-exposed laboratory animals have been equivocal and have not clearly demonstrated progression of the disease. In this study, morphometry and histopathology were used to assess emphysema in the lungs of B6C3F1 mice and Fischer-344 rats. The animals were exposed, whole-body, to CS at a concentration of 250 mg total particulate matter/m3 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 [Lm], volume density of alveolar air space [VVair]), and tissue loss (volume density of alveolar septa [VVspt]). In addition, centriacinar intra-alveolar inflammatory cells were counted to assess species differences in the type of inflammatory response associated with CS exposure. In mice, many of the morphometric parameters indicating emphysema differed significantly between CS-exposed and control animals. In CS-exposed rats, only some of the parameters differed significantly from control values. The Lm in both CS-exposed mice and rats was increased at 7 and 13 months, indicating an enlargement of parenchymal air spaces, but the VVair was increased significantly only in CS-exposed mice. The VVspt was decreased at both time points in mice, but not in rats, indicating damage to the structural integrity of parenchyma. Morphologic evidence of tissue destruction in the mice included alveoli that were irregular in size and shape and alveoli with multiple foci of septal discontinuities and isolated septal fragments. Morphometric differences in the mice at 13 months were greater than at 7 months, suggesting a progression of the disease. Inflammatory lesions within the lungs of mice contained significantly more neutrophils than those lesions in rats. These results suggest that B6C3F1 mice are more susceptible than F344-rats to the induction of emphysema by this CS exposure regimen and that in mice the emphysema may be progressive. Furthermore, the type of inflammatory response may be a determining factor for species differences in susceptibility to emphysema induction by CS exposure.
March
T H
TH
Inhalation Toxicology Laboratory, Lovelace Respiratory Research Institute, Albuquerque, New Mexico 87185, USA. tmarch@lrri.org
Barr
E B
EB
Finch
G L
GL
Hahn
F F
FF
Hobbs
C H
CH
Ménache
M G
MG
Nikula
K J
KJ
D000818:Animals; D003433:Crosses, Genetic; D004195:Disease Models, Animal; D004198:Disease Susceptibility; D005260:Female; D008168:Lung / Q000473:pathology; D008264:Macrophages / Q000473:pathology; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D009504:Neutrophils / Q000473:pathology; D010947:Plants, Toxic; D011656:Pulmonary Emphysema / Q000209:etiology* / Q000473:pathology; D051381:Rats; D011916:Rats, Inbred F344; D012906:Smoke / Q000009:adverse effects*; D013045:Species Specificity; D014026:Nicotiana; D015430:Weight Gain
D012906:Smoke