| Animal Models of Beryllium-induced Lung Disease Gregory L. Finch, Mark D. Hoover, Fletcher F. Hahn,
Kristen J. Nikula, Steven A. Belinsky, Patrick J. Haley,*
and William C. Griffith Inhalation Toxicology Research Institute, Albuquerque, New Mexico Abstract
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°C. At similar lung burdens, the 500°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°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 µg Be/g lung, inhaled Be metal induced benign and/or malignant lung tumors in over 50% of male and female F344 rats surviving  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 µg (~300 µg 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. -- Environ Health Perspect 104(Suppl 5) :973-979 (1996) Key words: beryllium, inhalation, beagle dogs, monkeys, rats, mice, granuloma, lymphocyte proliferation, cancer
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