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  • Title: Enhanced pulmonary epithelial replication and axial airway mucosubstance changes in F344 rats exposed short-term to mainstream cigarette smoke.
    Author: March TH, Kolar LM, Barr EB, Finch GL, Ménache MG, Nikula KJ.
    Journal: Toxicol Appl Pharmacol; 1999 Dec 01; 161(2):171-9. PubMed ID: 10581211.
    Abstract:
    Cigarette smoking is associated with respiratory diseases that may be caused by injury to specific pulmonary cells. The injury may manifest itself as site-specific enhanced cellular replication. In this study, rats were exposed either to mainstream cigarette smoke (CS; 250 mg total particulate matter/m(3)) or to filtered air (FA) for 6 h/day, 5 days/week, for 2 weeks. In one group, cells in S-phase were labeled over 7 days by bromodeoxyuridine (BrdU) released from implanted osmotic pumps (pump labeled), while another group received BrdU by injection 2 h prior to necropsy (pulse labeled). Morphometry showed that the type II epithelial BrdU labeling index (LI) was significantly elevated in the CS-exposed animals of both labeling groups. The axial airway and terminal bronchiolar LIs were enhanced by CS only in the pump-labeled group. In a third group (pulse labeled), 2 weeks of recovery following exposure to CS allowed a normalization in the type II LI. In the pump-labeled rats, the CS-induced elevation of the type II LI was greater than the LI elevation in conducting airways, suggesting that the parenchyma may have been injured more than the conducting airways. The terminal bronchiolar LI in the pump-labeled group, regardless of exposure, was significantly greater than the axial airway LI. Pump labeling, in contrast to pulse labeling, could therefore discern differences among replication rates of conducting airway epithelium in different regions of the lung. Mucosubstance (MS) within the axial airway epithelium was quantified by morphometry. The CS exposure did not increase the total number of MS-containing cells or the total number of axial airway epithelial cells, but there was a phenotype change in the MS cells. Neutral MS cells (periodic acid-Schiff-positive) were significantly decreased, while acid MS cells (alcian blue-positive) were slightly increased by CS exposure. Either cell replication and differentiation or differentiation alone may have changed the phenotype in the MS cell population.
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