Exposure to beryllium (Be) is an occupational hazard that can cause chronic beryllium disease (CBD), an irreversible, debilitating granulomatous lung disease, in as many as 3-5% of exposed workers. CBD begins as an MHC Class II-restricted, Th1 hypersensitivity. CBD can be viewed as a biphasic disease: first peripheral sensitization occurs, and then, in some, there is progression to pulmonary granuloma formation. In order to look at both aspects of the disease, we performed a mouse ear-swelling test (MEST) to correlate with the sensitization process and a 5-month oropharyngeal aspiration study to look at granuloma development in mice. In the MEST, 21 different inbred mouse strains were utilized to see if they would exhibit varying hypersensitivity responses to Be. In two separate experiments, mice were placed into either group: C/C group (sensitized with vehicle, challenged with vehicle) or Be/Be group (sensitized with beryllium sulfate, challenged with beryllium sulfate). The SJL/J strain appeared to exhibit one of the greatest hypersensitivity responses with a 37.7% increase over the baseline ear thickness in the Be/Be group compared with a 2.6% increase in the control group. The FVB/N strain, in contrast, had statistically insignificant, increases in ear thickness. The results for the hypersensitivity MEST response were as follows: SJL/J, AKR, DBA/2J>>PL/J, LG/J, MRL/MpJ>> FVB/N, 129/SvlmJ, SWR/J. The data have been analyzed by haplotype mapping to uncover genes associated with sensitization to beryllium. In the aspiration study, seven inbred strains aspirated either 20µg, 35µg, or 50µg of beryllium metal powder or water vehicle monthly. Clear dose and strain differences in beryllium-induced lymphogranulomatus nodules were observed. Uncovering the genes responsible for the hypersensitive phenotype and granuloma formation in mice may prove useful in learning more about the mechanisms involved in CBD.
The Toxicologist. Society of Toxicology 46th Annual Meeting and ToxExpo, March 25-29, 2007, Charlotte, North Carolina