SENSITIVITY OF HUMAN-CELLS TO MILD HYPERTHERMIA

The cytotoxic effects of short duration. high temperature, and long du ration, low temperature hyperthermia were determined in human cells gr owing in culture. The human tumor cell lines A549 (lung carcinoma), Wi Dr (colon carcinoma), and U87MG (glioblastoma) were used. In addition, a normal human lung fibroblast cell type 18Lu was used. Sensitivity t o direct cell killing was measured at 41, 43, and 45-degrees-C. Heat i nduced perturbations of cell cycle and proliferation were also analyze d. The results obtained on sensitivity of the above human cell lines a t 43 and 45-degrees-C are similar to those of the previous work of oth ers in that the human cell lines were observed to be relatively resist ant to thermal killing at 43 or 45-degrees-C, when compared to heat se nsitive rodent cell lines. The comparison is important because most pr ior hyperthermic research has been performed with rodent cells and cli nical protocols have been designed with the use of rodent data. In con trast to the 43-degrees-C response, most of the human cells we tested were killed by 41-degrees-C heating to an extent greater than that obs erved for rodent cells. The heat sensitivities of the four different h uman cell lines varied widely. This appeared to be due to differences in both intrinsic heat sensitivity and tolerance development. During 4 1-degrees-C heating, human cells did not proliferate and cell cycle pe rturbations developed but did not correlate with sensitivity to killin g. Our heat sensitivity measurements point out the shortcomings of usi ng data derived from rodent systems to predict clinical outcome of hyp erthermia therapy.