Recovery of CHO Cells from Hyperthermic Potentiation to X Rays: Repair of DNA and Chromatin

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Abstract
Above the critical temperature, about 42.5.degree. C, hyperthermic potentiation of Chinese hamster ovary (CHO) cells to X irradiation was accompanied by increased binding of nonhistone proteins to DNA and by reduced rates of rejoining of DNA strand breaks. These biochemical changes were reversed as the cells recovered from the hyperthermic exposure at 37.degree. C. When, e.g., CHO cells were held at 45.5.degree. C for 17 min the ratio of nonhistone protein to DNA increased 2-fold and the time taken to rejoin half the DNA strand breaks induced by X irradiation increased more than 3-fold. If the hyperthermically treated cells were incubated at 37.degree. C before X irradiation, the ratio of nonhistone protein to DNA returned to normal in 12 h but the depressed rate of rejoining of DNA strand breaks and increased cell radiosensitivity remained unaltered. Cell radiosensitivity began to decrease after 12 h and recovery from hyperthermia-potentiated radiosensitivity was complete by 48 h. In the same interval the rate of rejoining of DNA strand breaks returned to normal. The reduction in the rate of rejoining of DNA strand breaks apparently involved changes in DNA structure (perhaps the supercoiling) which were restored only after the thermal enhancement of protein binding was reversed. The reduction in enzyme activity probably resulted from decreased enzyme-substrate affinity not denaturation of enzyme molecules per se. Critical hyperthermic potentiation (i.e., above 42.5.degree. C for CHO cells may have logistical advantages over subcritical hyperthermic potentiation (i.e., below 42.5.degree. C) in clinical situations for treatment of malignancies.