Griffiths G D, Lindsay C D, Upshall D G
Chemical and Biological Defence Establishment, Porton Down, Salisbury, Wiltshire, UK.
Toxicology. 1994 May 31;90(1-2):11-27. doi: 10.1016/0300-483x(94)90201-1.
The bovine pulmonary endothelial (BPE) cell line was examined as a model to study the toxicity of ricin and abrin toxins currently under investigation. The BPE cell line was examined because ricin has been shown to bind to endothelial cells. Cell viability was assessed using several different biochemical parameters including growth (DNA by binding of gentian violet stain), mitochondrial function (succinate dehydrogenase activity) using MTT and lysosomal integrity (neutral red retention assay). In order to compare toxicities and investigate potential protective compounds, concentrations of toxins causing death of 50% and 70% of the (control) cell population (LC50 and LC70, respectively) were determined. It is concluded that while ricin and abrin share a common mechanism of action ricin is slightly less toxic than abrin. BPE cells are a good model for future mechanistic studies and particularly for initial phase screening of potentially therapeutic compounds. Carbohydrates were used in an attempt to examine which receptor types were involved in the binding and uptake of ricin and abrin by the cell line. It was found that only high concentrations of galactose prevented lethality while mannose apparently had no effect. Furthermore, the molar excess of carbohydrate to toxin required in order to achieve protection indicated that this would be an impractical approach to adopt in vivo.
牛肺内皮（BPE）细胞系作为一种模型，用于研究目前正在研究的蓖麻毒素和相思子毒素的毒性。选用BPE细胞系是因为已证明蓖麻毒素能与内皮细胞结合。使用几种不同的生化参数评估细胞活力，包括生长情况（通过结合龙胆紫染色检测DNA）、使用MTT检测线粒体功能（琥珀酸脱氢酶活性）以及溶酶体完整性（中性红保留试验）。为了比较毒性并研究潜在的保护化合物，测定了导致50%和70%（对照）细胞群体死亡的毒素浓度（分别为LC50和LC70）。得出的结论是，虽然蓖麻毒素和相思子毒素有共同的作用机制，但蓖麻毒素的毒性略低于相思子毒素。BPE细胞是未来进行作用机制研究的良好模型，尤其适用于对潜在治疗化合物的初步筛选。尝试使用碳水化合物来研究该细胞系中蓖麻毒素和相思子毒素的结合及摄取涉及哪些受体类型。发现只有高浓度的半乳糖能防止细胞死亡，而甘露糖显然没有作用。此外，为实现保护所需的碳水化合物与毒素的摩尔过量表明，这在体内将是一种不切实际的方法。
