Finch G L, Hoover M D, Hahn F F, Nikula K J, Belinsky S A, Haley P J, Griffith W C
Inhalation Toxicology Research Institute, Albuquerque, New Mexico 87185, USA.
Environ Health Perspect. 1996 Oct;104 Suppl 5(Suppl 5):973-9. doi: 10.1289/ehp.96104s5973.
The inhalation Toxicology Research Institute (ITRI) is conducting research to improve the understanding of chronic beryllium disease (CBD) and beryllium-induced lung cancer. Initial animal studies examined beagle dogs that inhaled BeO calcined at either 500 or 1000 degrees C. At similar lung burdens, the 500 degrees C BeO induced more severe and extensive granulomatous pneumonia, lymphocytic infiltration into the lung, and positive Be-specific lymphocyte proliferative responses in vitro than the 1000 degrees C BeO. However, the progressive nature of human CBD was not duplicated. More recently, Strains A/J and C3H/Hej mice were exposed to Be metal by inhalation. This produced a marked granulomatous pneumonia, diffuse infiltrates, and multifocal aggregates of interstitial lymphocytes with a pronounced T helper component and pulmonary in situ lymphocyte proliferation. With respect to lung cancer, at a mean lung burden as low as 17 micrograms Be/g lung, inhaled Be metal induced benign and/or malignant lung tumors in over 50% of male and female F344 rats surviving > or = 1 year on study. Substantial tumor multiplicity was found, but K-ras and p53 gene mutations were virtually absent. In mice, however, a lung burden of approximately 60 micrograms (-300 micrograms Be/g lung) caused only a slight increase in crude lung tumor incidence and multiplicity over controls in strain A/J mice and no elevated incidence in strain C3H mice. Taken together, this research program constitutes a coordinated effort to understand beryllium-induced lung disease in experimental animal models.
吸入毒理学研究所（ITRI）正在开展研究，以增进对慢性铍病（CBD）和铍诱导肺癌的了解。最初的动物研究检测了吸入在500或1000摄氏度下煅烧的氧化铍的比格犬。在肺部负荷相似的情况下，500摄氏度的氧化铍比1000摄氏度的氧化铍诱发更严重、更广泛的肉芽肿性肺炎、淋巴细胞浸润到肺部以及体外铍特异性淋巴细胞增殖反应呈阳性。然而，并未重现人类CBD的渐进性特征。最近，A/J和C3H/Hej品系的小鼠通过吸入接触金属铍。这导致了明显的肉芽肿性肺炎、弥漫性浸润以及间质淋巴细胞的多灶性聚集，伴有明显的辅助性T细胞成分和肺部原位淋巴细胞增殖。关于肺癌，在平均肺部负荷低至17微克铍/克肺的情况下，吸入金属铍在研究中存活≥1年的超过50%的雄性和雌性F344大鼠中诱发了良性和/或恶性肺部肿瘤。发现有大量肿瘤多发性，但几乎不存在K-ras和p53基因突变。然而，在小鼠中，肺部负荷约为60微克（-300微克铍/克肺）仅使A/J品系小鼠的粗肺癌发病率和多发性比对照组略有增加，而在C3H品系小鼠中发病率并未升高。总体而言，该研究项目是为了在实验动物模型中了解铍诱导的肺部疾病而进行的一项协同努力。
