Use of proliferation tests to evaluate the effects of complexing agents on beryllium toxicity
Article first published online: 12 SEP 2008
Copyright © 2008 John Wiley & Sons, Ltd.
Journal of Applied Toxicology
Volume 29, Issue 1, pages 27–35, January 2009
How to Cite
Stephan, C. H., Sauvé, S., Fournier, M. and Brousseau, P. (2009), Use of proliferation tests to evaluate the effects of complexing agents on beryllium toxicity. J. Appl. Toxicol., 29: 27–35. doi: 10.1002/jat.1378
- Issue published online: 4 DEC 2008
- Article first published online: 12 SEP 2008
- Manuscript Accepted: 8 JUL 2008
- Manuscript Revised: 27 JUN 2008
- Manuscript Received: 30 NOV 2007
- splenocyte proliferation test;
- chelation therapy
Occupational exposure to beryllium may cause chronic beryllium disease (CBD), a granulomatous interstitial pneumonitis caused by a cell-mediated immune response with delayed hypersensitivity initiated by an electrostatic interaction with the MHC class II human leukocyte antigen (HLA). Increased research efforts focus on the development of a CBD treatment by chelation therapy. This work presents an in vitro evaluation of the beneficial effects of beryllium chelation with different organic substrates. We have used a standard beryllium lymphocyte proliferation test (BeLPT) adapted for mouse splenocytes. Three complexing agents, 4,5-dihydroxy-1,3-benzenedisulfonic acid (tiron), nitrilotripropionic acid (NTP) and nitrilotriacetic acid (NTA), were tested using different protocols of the splenocyte proliferation test (SPT). We studied their corrective effect (beryllium pre-exposed splenocytes), their protective effect (ligand pre-exposed splenocytes) and their combined effects at fixed Be:L ratio of 1:2, at fixed Be concentration and at fixed L concentration. We also studied the effect of tiron in preventing splenocyte sensitization to beryllium. All three complexing agents showed a corrective effect and proved efficient in the combined effects, except NTA in the fixed Be:L ratio. Only NTP and tiron showed a significant protection at lower beryllium concentrations, while NTA was not significant. Splenocytes pre-exposed to chelated beryllium did not show sensitization while splenocytes pre-exposed to beryllium were sensitized. We observed a strong correlation between the efficiency of the complexing agent and its affinity towards beryllium. Both tiron and NTP showed a similar affinity towards the beryllium ion that is 107 higher than that of NTA. Copyright © 2008 John Wiley & Sons, Ltd.