Animal models of beryllium-induced lung disease.
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.
Finch
G L
GL
Inhalation Toxicology Research Institute, Albuquerque, New Mexico 87185, USA. gfinch@lucy.tli.org
Hoover
M D
MD
Hahn
F F
FF
Nikula
K J
KJ
Belinsky
S A
SA
Haley
P J
PJ
Griffith
W C
WC
D000818:Animals; D001608:Beryllium / Q000633:toxicity*; D004195:Disease Models, Animal; D004285:Dogs; D005260:Female; D006099:Granuloma / Q000139:chemically induced; D006801:Humans; D008171:Lung Diseases / Q000139:chemically induced*; D008175:Lung Neoplasms / Q000139:chemically induced; D008252:Macaca fascicularis; D008297:Male; D051379:Mice; D051381:Rats
D001608:Beryllium