Enhancement of the responses of human colon adenocarcinoma cells to X-irradiation and cis-platinum by N-methylformamide (NMF).

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.