Sanders C L, Lauhala K E, McDonald K E
Battelle, Pacific Northwest Laboratory, Biology and Chemistry Department, Richland, WA 99352.
Exp Lung Res. 1989 Sep;15(5):755-69. doi: 10.3109/01902148909062859.
The goal of this study is to show the relationship of inhaled Pu particle distribution and alveolar-bronchiolar target-cell response with respect to the formation of pulmonary carcinoma. The proliferation of type 2 alveolar epithelium and nonciliated bronchiolar epithelium appears critical in the induction of lung tumors associated from inhaled 239PuO2. Female, Wistar rats were either sham-exposed (40 rats) or given a single inhalation to 169Yb-239PuO2 (99 rats, ILB, 3.9 +/- 1.2 kBq) and examined at 20 time intervals from 1 day to 700 days postexposure for Pu particle distribution in airways by SEM quantitative autoradiography and for cell labeling with tritiated thymidine. Initially, deposited Pu particles were rapidly cleared from the surface of the trachea, bronchi, and bronchioles within a few days. Thereafter, about 5 times more alpha track exposure to the bronchiolar epithelium was delivered from Pu particles found in peribronchiolar alveoli than from Pu particles being cleared from bronchiolar surfaces. Exposure of bronchiolar epithelium at later times was due mostly to the formation of peribronchiolar Pu particle aggregates. A maximal increase in labeled alveolar wall cells was seen at 60 days after exposure, decreasing gradually to control levels by 400 days. Cell labeling in focal alveolar regions of Pu aggregation was about 5 fold higher. Increased bronchiolar epithelium labeling appeared in two phases. The first phase was seen 15 days after exposure, associated with initial deposition and clearance of Pu particles. The second phase slowly reached a maximum at 250 days and was associated with peribronchiolar Pu aggregate formation. The temporal-spatial dose-distribution pattern for inhaled Pu particles is an important aspect of Pu-induced pulmonary carcinogenesis.
本研究的目的是揭示吸入钚颗粒分布和肺泡 - 细支气管靶细胞反应与肺癌形成之间的关系。2型肺泡上皮和无纤毛细支气管上皮的增殖在吸入239PuO2所致的肺癌诱导中似乎至关重要。将雌性Wistar大鼠分为假暴露组（40只大鼠）或单次吸入169Yb - 239PuO2组（99只大鼠，内照射剂量，3.9±1.2 kBq），并在暴露后1天至700天的20个时间间隔进行检查，通过扫描电子显微镜定量放射自显影术观察气道中钚颗粒分布，并用氚标记胸腺嘧啶核苷进行细胞标记。最初，沉积的钚颗粒在几天内迅速从气管、支气管和细支气管表面清除。此后，细支气管周围肺泡中发现的钚颗粒对细支气管上皮的α径迹照射量比从细支气管表面清除的钚颗粒多约5倍。后期细支气管上皮的照射主要是由于细支气管周围钚颗粒聚集体的形成。暴露后60天可见标记的肺泡壁细胞数量最多，到400天时逐渐降至对照水平。钚聚集的局灶性肺泡区域的细胞标记约高5倍。细支气管上皮标记增加呈两个阶段。第一阶段在暴露后15天出现，与钚颗粒的初始沉积和清除有关。第二阶段在250天时缓慢达到最大值，与细支气管周围钚聚集体的形成有关。吸入钚颗粒的时空剂量分布模式是钚诱导肺癌发生的一个重要方面。
