Dixon D, Bowser A D, Badgett A, Haseman J K, Brody A R
Laboratory of Experimental Pathology, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA.
J Environ Pathol Toxicol Oncol. 1995;14(3-4):205-13.
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.
我们一直在研究暴露于石棉纤维气溶胶的啮齿动物肺部早期纤维增生性事件。在本文介绍的实验中，连续两次暴露于温石棉后，评估了小鼠肺部细支气管/肺泡（B/A）区域中溴脱氧尿苷（BrdU）的掺入情况。6至8周龄的雄性A/J品系小鼠，该品系B/A肿瘤的自发发生率较高，连续两天（每天3小时）吸入石棉纤维。在首次吸入石棉暴露48小时后，一组小鼠还接受了腹腔注射乌拉坦，这是一种已知的A/J小鼠肺癌致癌物。暴露于石棉的小鼠组在初次暴露后48小时、72小时和2周时，肺部B/A区域上皮和间质细胞核中BrdU的掺入量显著增加（p<0.05）。到1个月时，暴露于石棉的小鼠的标记指数与对照组在统计学上无显著差异；然而，在最初石棉沉积的主要部位，即第一肺泡管分叉（ALDB）区域，上皮和间质细胞仍可检测到标记。由于各导管之间存在相当大的变异性，在3个月时，暴露于石棉的小鼠与对照组之间没有统计学上的显著差异。我们得出结论，在A/J小鼠中，两次3小时吸入石棉暴露后在肺部B/A区域观察到的初始增殖反应在暴露后2周内显著延长。此外，在暴露后长达3个月的时间里，第一肺泡管分叉处的上皮和间质细胞中可测量到高于对照值的标记。吸入石棉暴露后给予乌拉坦，对肺部B/A区域任何细胞中BrdU的掺入没有明显影响。此外，尽管A/J品系对肺癌形成高度敏感，但未暴露的对照A/J小鼠未显示出细胞增殖的自发增加。
