Lundgren D L, Mauderly J L, Rebar A H, Gillett N A, Hahn F F
Inhalation Toxicology Research Institute, Lovelace Biomedical and Environmental Research Institute, Albuquerque, NM 87185.
Health Phys. 1991 Mar;60(3):353-63. doi: 10.1097/00004032-199103000-00004.
We investigated the modifying effects of preexisting, bleomycin-induced pulmonary fibrosis on the deposition, retention, and biological effects of inhaled 239PuO2 in the rat. Among rats exposed to similar airborne concentrations of 239PuO2, initial lung burdens of 239Pu per kilogram body mass were similar whether or not pulmonary fibrosis was present. However, clearance of 239Pu from the lungs was significantly decreased in the rats with preexisting pulmonary fibrosis. The incidence of lung lesions (epithelial hyperplasia, diffuse macrophage increases and aggregation, and loose and dense connective tissue) was significantly greater among rats with preexisting pulmonary fibrosis than among the exposed controls. Rats with preexisting fibrosis had shorter life spans than 239PuO2-exposed control rats. When groups of rats with similar alpha doses to the lungs were compared, the incidences of neoplastic lesions in the lung, the times to death of rats with lung neoplasms, and the risk of lung tumors per unit of alpha dose to the lungs in rats with or without pulmonary fibrosis were similar. The results of this study suggest that humans with uncomplicated pulmonary fibrosis may not be more sensitive to the carcinogenic effects of inhaled 239PuO2 than are individuals with normal lungs, assuming that the total alpha doses to the lungs are similar.
我们研究了博来霉素诱导的原有肺纤维化对大鼠吸入239PuO2的沉积、滞留及生物学效应的影响。在暴露于相似空气浓度239PuO2的大鼠中，无论是否存在肺纤维化，每千克体重的239Pu初始肺负荷相似。然而，原有肺纤维化的大鼠肺部239Pu的清除率显著降低。原有肺纤维化的大鼠肺部病变（上皮增生、弥漫性巨噬细胞增多和聚集以及疏松和致密结缔组织）的发生率明显高于暴露对照组。原有纤维化的大鼠寿命比暴露于239PuO2的对照大鼠短。当比较肺部接受相似α剂量的大鼠组时，有无肺纤维化的大鼠肺部肿瘤性病变的发生率、患肺肿瘤大鼠的死亡时间以及每单位肺部α剂量的肺肿瘤风险相似。本研究结果表明，假设肺部的总α剂量相似，单纯性肺纤维化患者对吸入239PuO2致癌作用的敏感性可能并不高于肺部正常的个体。
