Incorporation of bromodeoxyuridine (BrdU) in the bronchiolar-alveolar regions of the lungs following two inhalation exposures to chrysotile asbestos in strain A/J mice.

We have been studying early fibroproliferative events in the lungs of rodents exposed to aerosols of asbestos fibers. In the experiments presented here, incorporation of bromodeoxyuridine (BrdU) in the bronchiolar/alveolar (B/A) regions of the lungs in mice was assessed following two consecutive exposures to chrysotile asbestos. Six to 8-week-old male strain A/J mice, a strain with a high spontaneous incidence of B/A tumors, were exposed to inhaled asbestos fibers for two consecutive days (3 hours/day). A group of mice was also given an intraperitoneal injection of urethane, a known lung carcinogen in A/J mice, 48 h after initial inhalation exposure to asbestos. The groups of mice exposed to asbestos had significantly (p <0.05) increased incorporation of BrdU in the nuclei of epithelial and interstitial cells in the B/A regions of the lung at 48 h, 72 h, and 2 weeks after initial exposure. By 1 month, the labeling indices in mice exposed to asbestos were not statistically significantly different from the controls; however, in the regions of the first alveolar duct bifurcations (ALDB), the primary site of initial asbestos deposition, there continued to be detectable labeling of the epithelial and interstitial cells. Because of considerable variability from duct to duct, there were no statistically significant differences between the asbestos-exposed mice and control groups at 3 months. We conclude that in A/J mice the initial proliferative response observed in the B/A regions of the lung after two 3-h inhalation exposures to asbestos is significantly prolonged through 2 weeks post-exposure. In addition, there was measurable labeling above control values in the epithelial and interstitial cells of the first alveolar duct bifurcations up to 3 months after exposure. Urethane had no apparent effect on the incorporation of BrdU into any cells of the B/A regions of the lung when administered after inhalation exposure to asbestos. Furthermore, although the A/J strain is highly susceptible to lung tumor formation, the unexposed control A/J mice showed no spontaneous increases in cell proliferation.