Herbert R A, Gillett N A, Rebar A H, Lundgren D L, Hoover M D, Chang I Y, Carlton W W, Hahn F F
Inhalation Toxicology Research Institute, Albuquerque, New Mexico 87185.
Radiat Res. 1993 Apr;134(1):29-42.
Light microscopy, morphometry, and cytokinetic techniques were used to examine the dynamics of plutonium-induced pulmonary proliferative lesions and neoplasms in rats at several intervals to 450 days after inhalation exposure to aerosols of 239PuO2. Maximal increases in alveolar and bronchiolar epithelial cell labeling were seen at 30 days; decreasing subsequently, the levels remained elevated above control indices. Focal proliferative epithelial lesions developed in the lung by 180 days and before the onset of pulmonary neoplasms. Pulmonary neoplasms, predominantly adenocarcinomas and squamous cell carcinomas, were initially observed at 308 days. The proliferative lesions progressed through a succession of morphological changes leading to the development of neoplasms. The volume density (fraction) and epithelial surface area of foci of alveolar epithelial hyperplasia increased progressively between 180 and 450 days after exposure, in contrast to the other proliferative lesions. We conclude that plutonium-induced pulmonary neoplasms develop through a succession of focal proliferative lesions that represent developmental preneoplastic lesions. Progressive increases in volume and epithelial surface area of the alveolar epithelial hyperplasias suggest that they may be more at risk for neoplastic transformation than the other histological types of proliferative foci.
运用光学显微镜、形态测量学和细胞动力学技术，在吸入暴露于239PuO2气溶胶后的450天内，每隔一段时间对大鼠钚诱导的肺部增殖性病变和肿瘤的动态变化进行检查。肺泡和细支气管上皮细胞标记的最大增加出现在30天；随后下降，但仍高于对照指标。到180天时，肺部出现局灶性增殖性上皮病变，且早于肺部肿瘤的发生。肺部肿瘤主要为腺癌和鳞状细胞癌，最初在308天被观察到。增殖性病变经历了一系列形态学变化，导致肿瘤的发展。与其他增殖性病变相比，肺泡上皮增生灶的体积密度（分数）和上皮表面积在暴露后180至450天之间逐渐增加。我们得出结论，钚诱导的肺部肿瘤通过一系列局灶性增殖性病变发展而来，这些病变代表发育性癌前病变。肺泡上皮增生灶的体积和上皮表面积的逐渐增加表明，它们比其他组织学类型的增殖灶更易发生肿瘤转化。
