Aspects of biochemical effects by hyperthermia.

Hyperthermia caused an immediate decrease of DNA, RNA, and protein synthesis. The latter process was most sensitive. Initiation of DNA synthesis at the transition from G1-to S-phase and at the start of new replication units were inhibited. These effects were responsible for the growth delay of cells and were potentiated with irradiation. The immediate inhibition of protein synthesis was due mainly to a disaggregation of the synthesizing mechanisms. It led to a decrease of enzyme activities with a short biological half-life, e.g., ornithine decarboxylase. Lysosomal hydrolytic activities might be enhanced after hyperthermia and contribute to tissue damage. During hyperthermia, glycogen breakdown and glucose turnover through glycolysis and the citrate cycle were apparently increased, but after hyperthermia, respiration and glycolysis were reduced. No lactate accumulation occurred, but other acidic metabolites were enhanced and could induce a metabolic acidosis hours later. A glucose load potentiated the effects on respiration and glycolysis. Immediately after hyperthermia, a lactate accumulation was observed under these conditions. A formula is given by which the ratios of reduced to oxidized substrates might indicate the redox state in different cellular compartments, with oxygen pressure, and during other metabolic conditions. Such changes of the intracellular milieu are important for the thermosensitivity of cells.