Baseman J B, Pappenheimer A M, Gill D M, Harper A A
J Exp Med. 1970 Dec 1;132(6):1138-52. doi: 10.1084/jem.132.6.1138.
The blood clearance and distribution in the tissues of (125)I after intravenous injection of small doses (1.5-5 MLD or 0.08-0.25 microg) of (125)I-labeled diphtheria toxin has been followed in guinea pigs and rabbits and compared with the fate of equivalent amounts of injected (125)I-labeled toxoid and bovine serum albumin. Toxoid disappeared most rapidly from the blood stream and label accumulated and was retained in liver, spleen, and especially in kidney. Both toxin and BSA behaved differently. Label was found widely distributed among all the organs except the nervous system and its rate of disappearance from the tissues paralleled its disappearance from the circulation. There was no evidence for any particular affinity of toxin for muscle tissue or for a "target" organ. Previous reports by others that toxin causes specific and selective impairment of protein synthesis in muscle tissue were not confirmed. On the contrary, both in guinea pigs and rabbits, a reduced rate of protein synthesis was observed in all tissues that had taken up the toxin label. In tissues removed from intoxicated animals of both species there was an associated reduction in aminoacyl transferase 2 content. It is concluded that the primary action of diphtheria toxin in the living animal is to effect the inactivation of aminoacyl transferase 2. The resulting inhibition in rate of protein synthesis leads to morphologic damage in all tissues reached by the toxin and ultimately to death of the animal.
给豚鼠和兔子静脉注射小剂量（1.5 - 5 MLD或0.08 - 0.25微克）的¹²⁵I标记的白喉毒素后，对¹²⁵I在血液中的清除及在组织中的分布情况进行了追踪，并与等量注射的¹²⁵I标记类毒素和牛血清白蛋白的去向进行了比较。类毒素从血流中消失得最快，标记物在肝脏、脾脏尤其是肾脏中积累并保留。毒素和牛血清白蛋白的表现则不同。除神经系统外，标记物在所有器官中广泛分布，其从组织中的消失速率与其从循环中的消失速率平行。没有证据表明毒素对肌肉组织或“靶”器官有任何特殊亲和力。其他人先前关于毒素导致肌肉组织中蛋白质合成特异性和选择性受损的报道未得到证实。相反，在豚鼠和兔子中，摄取毒素标记物的所有组织中蛋白质合成速率均降低。在从这两个物种的中毒动物身上取出的组织中，氨酰基转移酶2含量也相应降低。结论是，白喉毒素在活体动物中的主要作用是使氨酰基转移酶2失活。由此导致的蛋白质合成速率抑制会使毒素到达的所有组织发生形态学损伤，最终导致动物死亡。
