Gabliks J, Falconer M
J Exp Med. 1966 Apr 1;123(4):723-32. doi: 10.1084/jem.123.4.723.
The cytotoxicity (TD) level of diphtheria toxin for human Chang liver strain was 0.1 guinea pig MLD per ml; for mouse liver NCTC 1469 strain, the TD was 500 MLD per ml. The results of cell culture toxicity correlated well with relative susceptibility of both man and mouse. The initial effects of toxin on the susceptible Chang liver cells were studied at one half the TD level (0.05 MLD per ml). At this low concentration of toxin, the number of cells per culture was reduced slightly below the "0" hr values, whereas the amounts of cell protein, RNA, and DNA were increased. Analysis of the toxin-treated cells indicated an enlargement of the cells. The individual cells contained significantly more protein, RNA, and DNA than the control cells and the cell volume was increased 1.9 times. When purified diphtheria toxin was incubated with the susceptible Chang liver cells and then tested for its biological activity, the results showed an increased diffusion rate in parabiotic culture chambers and definite cytotoxicity to the normally resistant mouse liver cells. The cytotoxicity was neutralizable with antitoxin. The results suggest that the toxin-susceptible cells transform the toxin molecule to a more active derivative which affects the highly resistant mouse liver cell.
白喉毒素对人张氏肝细胞株的细胞毒性（TD）水平为每毫升0.1豚鼠最小致死量；对小鼠肝NCTC 1469株，TD为每毫升500最小致死量。细胞培养毒性结果与人及小鼠的相对易感性密切相关。在TD水平的一半（每毫升0.05最小致死量）下研究了毒素对敏感的张氏肝细胞的初始作用。在这种低浓度毒素作用下，每个培养物中的细胞数量略低于“0”小时的值，而细胞蛋白质、RNA和DNA的量却增加了。对毒素处理细胞的分析表明细胞增大。单个细胞所含的蛋白质、RNA和DNA比对照细胞明显更多，细胞体积增加了1.9倍。当将纯化的白喉毒素与敏感的张氏肝细胞一起孵育，然后检测其生物活性时，结果显示在联体培养室中的扩散速率增加，并且对正常抗性的小鼠肝细胞具有明确的细胞毒性。这种细胞毒性可用抗毒素中和。结果表明，毒素敏感细胞将毒素分子转化为一种更具活性的衍生物，该衍生物会影响高度抗性的小鼠肝细胞。
