Metabolic aspects of the role of hyperthermia im mammalian cell inactivation and their possible relevance to cancer treatment.

Abstract

Summary The importance of the metabolic state of Chinese hamster cells (HA1) in relation to the sensitivity of the cells to supranormal heat shock (43°) was investigated, and the following results were noted. 1.The sensitivity of cells to hyperthermia (as well as their ability to repair heat-induced damage after 43°) is strongly related to their nutritional history. Chinese hamster cells chronically deprived of serum (and probably other medium components) become extremely heat sensitive. 2.The role of oxygen and glucose may be less important; chronic or acute deprivation of oxygen has only minor influence on survival of exponentially growing or plateauphase cells. Similar conclusions appear to be true for variations in available glucose concentrations. 3.An appreciable fraction of cells killed by heat in the absence of serum lyse either during or shortly after heat exposure. The presence of serum inhibits the lysis process. 4.At temperatures of 41–43°, cells are sensitized to the chemotherapeutic agents, nitrogen mustard and bleomycin, but not to a nitrosourea. This sensitization may be related to repair inhibition at the elevated temperatures. The importance of these findings in the possible utilization of hyperthermia as an adjunct to conventional therapy is discussed.