Fodstad O, Johannessen J V, Schjerven L, Pihl A
J Toxicol Environ Health. 1979 Nov;5(6):1073-84. doi: 10.1080/15287397909529815.
Mice and dogs, were treated iv with the cytostatic proteins abrin and ricin and observed for clinical, biochemical, and morphological aberrations. In both mice and dogs death occurred within a narrow dose range. Dogs given toxic doses of ricin and abrin showed weakness, anorexia, apathy, and moderate fever. No signs attributable to the central nervous system were observed. Dogs dying from intoxication expired after 15-40 h. After nonlethal doses the animals recovered, apparently completely, in 1-3 wk. No delayed changed were observed in dogs after 4 mo. Abrin and ricin, in contrast to most other cytostatic agents, did not inhibit myelopolesis. However, after sublethal dpses a rapid but translent decrease of peripheral thrombocytes was observed. No evidence for specific liver damage or impairment of kidney function was obtained. Few abnormalities were observed at autopsy or on microscopic and electron microscopic examination of the tissues, in contrast to the findings of some earlier investigators. The results indicate that in mice and dogs given sublethal doses of highly purified toxins the symptoms are reversible. There was no finding militating against a phase 1 clinical trial.
给小鼠和狗静脉注射细胞抑制蛋白相思子毒素和蓖麻毒素,并观察其临床、生化和形态学异常。在小鼠和狗中,死亡均发生在狭窄的剂量范围内。给予蓖麻毒素和相思子毒素中毒剂量的狗表现出虚弱、厌食、冷漠和中度发热。未观察到归因于中枢神经系统的体征。死于中毒的狗在15 - 40小时后死亡。给予非致死剂量后,动物在1 - 3周内明显完全恢复。4个月后在狗身上未观察到延迟变化。与大多数其他细胞抑制药物不同,相思子毒素和蓖麻毒素不抑制骨髓生成。然而,在给予亚致死剂量后,观察到外周血小板迅速但短暂减少。未获得特定肝脏损伤或肾功能损害的证据。与一些早期研究者的发现相反,在尸检或对组织进行显微镜和电子显微镜检查时几乎未观察到异常。结果表明,给小鼠和狗给予亚致死剂量的高度纯化毒素后,症状是可逆的。没有不利于进行1期临床试验的发现。