Leith J T, Lee E S, Vayer A J, Dexter D L, Glicksman A S
Int J Radiat Oncol Biol Phys. 1985 Nov;11(11):1971-6. doi: 10.1016/0360-3016(85)90279-2.
The ability of the maturational agent N-methylformamide (NMF) to modify the response of exponentially growing clone A human colon adenocarcinoma cells to x-irradiation, cis-platinum (cis-DDP), or x-irradiation combined with cis-platinum was studied using an in vitro clonogenic assay. When clone A tumor cells were adaptively grown in medium containing 1% NMF (V/V) for 3 passages prior to experiments, a significantly increased sensitivity to x-irradiation as compared to non-NMF treated cells was found. This increased sensitivity was most marked in the low dose region of the survival curve (as indicated by a large increase in the alpha constant in the linear-quadratic equation), and is similar to the increased radiosensitivity observed after treatment of these tumor cells with N,N-dimethylformamide (DMF). Growth in NMF medium also sensitized these cells to the cytotoxic effects of a 1 hr treatment with cis-DDP at 37 degrees C. A dose enhancement factor of about 1.8 was found at the 10% level of survival for the NMF adapted and cis-DDP treated cells as compared to control cells. Clone A cells were treated either immediately prior to or immediately after x-irradiation with a single low dose of cis-DDP (1.5 microgram/ml, 1 hour at 37 degrees C) after adaptation to growth in NMF containing medium, and the modification of the X ray survival curve was compared to cells not exposed to NMF and to NMF-treated cells also treated with cis-DDP. For the non-NMF treated cells, the low dose cis-DDP treatment produced no change in the survival parameters of the X ray survival curve. However, the NMF adapted cells exhibited an additional decrement in cell survival, indicating that the effect of NMF on radiation on cis-DDP cell killing was additive in nature when all 3 agents were combined in this protocol. Also, there was no difference between the sequences of cis-DDP (1 hr, 37 degrees C) + X rays versus X rays + cis-DDP (1 hr, 37 degrees C). These data indicate that combinations of differentiation inducing agents, together with chemotherapeutic agents and X rays, may be a promising avenue of investigation in developing strategies for cancer treatment.
使用体外克隆形成试验研究了成熟因子N-甲基甲酰胺（NMF）改变指数生长的克隆A人结肠腺癌细胞对X射线、顺铂（顺式-DDP）或X射线联合顺铂反应的能力。当克隆A肿瘤细胞在实验前于含1%NMF（V/V）的培养基中适应性生长3代时，发现与未用NMF处理的细胞相比，其对X射线的敏感性显著增加。这种增加的敏感性在存活曲线的低剂量区域最为明显（线性二次方程中的α常数大幅增加表明），并且类似于用N，N-二甲基甲酰胺（DMF）处理这些肿瘤细胞后观察到的放射敏感性增加。在NMF培养基中生长也使这些细胞对在37℃下用顺式-DDP处理1小时的细胞毒性作用敏感。与对照细胞相比，对于适应NMF并经顺式-DDP处理的细胞，在10%存活水平时发现剂量增强因子约为1.8。在适应于在含NMF的培养基中生长后，克隆A细胞在X射线照射之前或之后立即用单次低剂量的顺式-DDP（1.5微克/毫升，37℃1小时）处理，并将X射线存活曲线的改变与未暴露于NMF的细胞以及也用顺式-DDP处理的NMF处理细胞进行比较。对于未用NMF处理的细胞，低剂量顺式-DDP处理未使X射线存活曲线的存活参数发生变化。然而，适应NMF的细胞表现出细胞存活的额外减少，表明当在该方案中联合使用所有三种试剂时，NMF对辐射和顺式-DDP细胞杀伤的作用本质上是相加的。此外，顺式-DDP（1小时，37℃）+X射线与X射线+顺式-DDP（1小时，37℃）的顺序之间没有差异。这些数据表明，分化诱导剂与化疗药物和X射线的联合可能是开发癌症治疗策略的一个有前景的研究途径。
