In previous studies, we have found that combined treatment with
BCNU and
sodium cyanate could have a greater effect on the survival of mice bearing
B16 melanoma than treatment with either agent alone. With rat
hepatoma and human
colon cancer cells in culture, we have obtained evidence that the inhibition of cell proliferation by
sodium cyanate is greater at pH 6.6 than at pH 7.4. In the present work, the effects of combination treatments on the proliferation of
cancer cells were studied with
cyanate, pH,
BCNU, and
hyperthermia. With HT29 human
colon cancer cells, the inhibitory effect of
BCNU (50-100 micrograms/ml) was greater when the cells were treated at pH 6.6 than at pH 7.4. The influence of pH appeared to be absent or minimal at lower or higher concentrations of
BCNU. We confirmed our previous observation that the inhibition of proliferation of LS174T human
colon cancer cells is greater at pH 6.6 than at pH 7.4, and we observed an inhibitory effect of
BCNU (50 or 200 micrograms/ml). However, no more than additive effects were seen with combination treatment. An inhibitory effect of
hyperthermia was seen for the incorporation of [3H]-
leucine into
protein of rat
hepatoma cells (HTC) and for that of [3H]-
thymidine into
DNA of human
colon cancer (HT29) cells. In neither case was the effect of
hyperthermia significantly enhanced by treatment with
sodium cyanate beyond that seen with one of the treatments alone. The data confirmed that the inhibitory effect of
sodium cyanate on cell proliferation can be enhanced by a low pH but did not provide evidence for synergistic effects in combination with
BCNU or
hyperthermia.