Kirstein M, Fiers W, Baglioni C
J Immunol. 1986 Oct 1;137(7):2277-80.
L929 cells were growth-inhibited after 1 to 2 days of treatment with human recombinant tumor necrosis factor (rTNF). This effect of rTNF was largely reversible, and L929 cells resumed normal growth when rTNF was removed. The rTNF showed growth inhibitory and cytotoxic activity when L929 cells approached a high cell density and grew slowly. This was shown in experiments in which L929 cells approached confluency at different times after being seeded at increasing initial densities. The rTNF had little effect on the growth of cells seeded at the lowest density tested. L929 cells cultured to high density synthesized RNA at a reduced rate. This suggested that a reduced rate of RNA synthesis may be at least in part responsible for the growth inhibitory and cytotoxic activities of rTNF on cells grown to high density. Treatment with inhibitors of RNA synthesis potentiated the cytotoxic activity of rTNF. Inhibition of mRNA synthesis was apparently responsible for the enhanced sensitivity to rTNF, as shown by experiments with 5,6-dichloro-1-beta-D-ribofuranosylbenzimidazole, an inhibitor of the synthesis of poly(A)-containing RNA.
用重组人肿瘤坏死因子（rTNF）处理1至2天后，L929细胞的生长受到抑制。rTNF的这种作用在很大程度上是可逆的，去除rTNF后，L929细胞恢复正常生长。当L929细胞接近高细胞密度且生长缓慢时，rTNF表现出生长抑制和细胞毒性活性。这在实验中得到了证明，即L929细胞在以增加的初始密度接种后，在不同时间接近汇合状态。rTNF对以测试的最低密度接种的细胞生长几乎没有影响。培养至高密度的L929细胞以降低的速率合成RNA。这表明RNA合成速率降低可能至少部分地导致了rTNF对高密度生长细胞的生长抑制和细胞毒性活性。用RNA合成抑制剂处理可增强rTNF的细胞毒性活性。如用5,6-二氯-1-β-D-呋喃核糖基苯并咪唑（一种含聚（A）RNA合成抑制剂）进行的实验所示，mRNA合成的抑制显然是对rTNF敏感性增强的原因。
