Mild hyperthermia as a potential mechanism to locally enhance cell growth kinetics

The effect of mild hyperthermia on growth kinetics of two human glioma and one mouse fibroblast cell line was evaluated over a 12 h (short-term) or 7 day (long-term) period. All cell lines showed growth enhancement at 38 degrees C, although the effect in C3H 10T(1)/(2) mouse fibroblasts was more pronounced and had a more rapid onset than in U87MG or LN71 glioma cells. At 39 degrees C, growth of C3H 10T(1)/(2) cells was slightly reduced and glioma cell lines similar to that of their respective 37 degrees C controls. At 40 degrees C, C3H 10T(1)/(2) cells showed a more rapid and dramatic growth reduction than glioma cell lines and accumulated in both G(0),/G(1) and G(2) checkpoint compartments. In contrast, U87MG cells accumulated only in G(2) and LN71 showed no checkpoint accumulation. The findings indicate that cell lines are differentially responsive to small temperature elevations. If similar differences exist between normal and diseased human tissues, local application of mild hyperthermia might offer a noninvasive and cost-effective method to achieve local enhancement of drugs that target proliferating tissue.