PMID- 18785683
OWN - NLM
STAT- MEDLINE
DCOM- 20090319
LR  - 20131121
IS  - 0260-437X (Print)
IS  - 0260-437X (Linking)
VI  - 29
IP  - 1
DP  - 2009 Jan
TI  - Use of proliferation tests to evaluate the effects of complexing agents on 
      beryllium toxicity.
PG  - 27-35
LID - 10.1002/jat.1378 [doi]
AB  - 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 10(7) higher than that of NTA.
CI  - Copyright (c) 2008 John Wiley & Sons, Ltd.
FAU - Stephan, Chadi H
AU  - Stephan CH
AD  - Department of Chemistry, Universite de Montreal, succ. Centre-Ville, Montreal, 
      QC, Canada H3C 3J7.
FAU - Sauve, Sebastien
AU  - Sauve S
FAU - Fournier, Michel
AU  - Fournier M
FAU - Brousseau, Pauline
AU  - Brousseau P
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - J Appl Toxicol
JT  - Journal of applied toxicology : JAT
JID - 8109495
RN  - 0 (Chelating Agents)
RN  - 01UQ1KPC7E (beryllium sulfate)
RN  - 4X87R5T106 (1,2-Dihydroxybenzene-3,5-Disulfonic Acid Disodium Salt)
RN  - KA90006V9D (Nitrilotriacetic Acid)
RN  - OW5102UV6N (Beryllium)
SB  - IM
MH  - 1,2-Dihydroxybenzene-3,5-Disulfonic Acid Disodium Salt/chemistry/pharmacology
MH  - Animals
MH  - Berylliosis/*immunology/prevention & control
MH  - Beryllium/chemistry/*toxicity
MH  - Cell Proliferation/drug effects
MH  - Cell Survival/drug effects
MH  - Cells, Cultured
MH  - Chelating Agents/chemistry/*pharmacology
MH  - Dose-Response Relationship, Drug
MH  - Female
MH  - Lymphocyte Activation/drug effects/immunology
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Nitrilotriacetic Acid/chemistry/pharmacology
MH  - Spleen/*drug effects/pathology
EDAT- 2008/09/13 09:00
MHDA- 2009/03/20 09:00
CRDT- 2008/09/13 09:00
PHST- 2008/09/13 09:00 [entrez]
PHST- 2008/09/13 09:00 [pubmed]
PHST- 2009/03/20 09:00 [medline]
AID - 10.1002/jat.1378 [doi]
PST - ppublish
SO  - J Appl Toxicol. 2009 Jan;29(1):27-35. doi: 10.1002/jat.1378.