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Title: Animal models of beryllium-induced lung disease

Journal Article · · Environmental Health Perspectives
DOI:https://doi.org/10.2307/3433020· OSTI ID:530620
; ;  [1]
  1. Inhalation Toxicology Research Institute, Albuquerque, NM (United States); and others

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 pg Be/g lung, inhaled Be metal induced benign and/or malignant lung tumors in over 50% of male and female F344 rats surviving {ge}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 {mu}g ({approximately}300 {mu}g 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. 47 refs., 1 fig., 3 tabs.

Sponsoring Organization:
USDOE
DOE Contract Number:
AC04-76EV01013
OSTI ID:
530620
Report Number(s):
CONF-9504282-; ISSN 0091-6765; TRN: 97:001285-0016
Journal Information:
Environmental Health Perspectives, Vol. 104, Issue Suppl.5; Conference: Air toxics: biomarkers in environmental applications, Houston, TX (United States), 27-28 Apr 1995; Other Information: PBD: Oct 1996
Country of Publication:
United States
Language:
English