Gd. Griffiths et al., EXAMINATION OF THE TOXICITY OF SEVERAL PROTEIN TOXINS OF PLANT-ORIGINUSING BOVINE PULMONARY ENDOTHELIAL-CELLS, Toxicology, 90(1-2), 1994, pp. 11-27
The bovine pulmonary endothelial (BPE) cell line was examined as a mod
el to study the toxicity of ricin and abrin toxins currently under inv
estigation. The BPE cell line was examined because ricin has been show
n to bind to endothelial cells. Cell viability was assessed using seve
ral different biochemical parameters including growth (DNA by binding
of gentian violet stain), mitochondrial function (succinate dehydrogen
ase activity) using MTT and lysosomal integrity (neutral red retention
assay). In order to compare toxicities and investigate potential prot
ective compounds, concentrations of toxins causing death of 50% and 70
% of the (control) cell population (LC(50) and LC(70), respectively) w
ere determined. It is concluded that while ricin and abrin share a com
mon mechanism of action ricin is slightly less toxic than abrin. BPE c
ells are a good model for future mechanistic studies and particularly
for initial phase screening of potentially therapeutic compounds. Carb
ohydrates were used in an attempt to examine which receptor types were
involved in the binding and uptake of ricin and abrin by the cell lin
e. It was found that only high concentrations of galactose prevented l
ethality while mannose apparently had no effect. Furthermore, the mola
r excess of carbohydrate to toxin required in order to achieve protect
ion indicated that this would be an impractical approach to adopt in v
ivo.