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Triggering of DNA Strand Breaks by 45°C Hyperthermia and Its Influence on the Repair of -Radiation Damage in Human White Blood Cells¹

Radiation Biology Branch, Health Sciences Division, Atomic Energy of Canada Limited, Chalk River Nuclear Laboratories, Chalk River, Ontario K0J 1J0, Canada

Human peripheral white blood cells, freshly isolated from normal individual donors, were exposed to hyperthermia. Heatgenerated DNA strand break damage and white blood cell capacity to repair radiation-induced breaks were determined by a fluorometric alkaline unwinding assay. Strand breaks could be readily detected when white blood cells were incubated in a physiological salt solution at temperatures between 41° and 46°C, for times up to 90 min. The time course of strand break induction at 45°C was characterized by a short initial lag, followed by a period of rapid break induction and subsequently a lower rate. Evidence is presented which suggests that the induction of DNA damage involved a "triggering" mechanism; a short treatment at 45°C (10 to 20 min) initiated a cellular event which led to a rapid increase in the number of strand breaks during subsequent incubation of 37°C. Continuous incubation at 45°C produced less DNA damage than an initial period at 45°C followed by incubation at 37°C. This apparent "triggering phenomenon" was not due to a triggering of the respiratory burst in phagocytic cells, since no could be detected; in fact, a 30-min treatment at 45°C largely blocked the capacity of the cells to respond normally to a soluble stimulator of the respiratory burst. Unlike -ray-induced breaks, 45°C hyperthermia-induced breaks did not rejoin during subsequent incubation for up to 1 h at 37°C. Additionally, 45°C hyperthermia treatment progressively inhibited the ability of the cells to repair subsequent -ray-induced breaks (4 Gy). This inhibition occurred during the period in which 45°C heat rapidly induced strand breaks. Hyperthermia (41°C), which did not trigger strand breaks, did not cause detectable inhibition of this repair capacity. There was no indication that hyperthermia sensitized cells to radiation-induced strand breaks.

¹ These data were presented, in substance, at the North American Hyperthermia Group meeting, Salt Lake City, UT, 1982 (12).

² To whom requests for reprints should be addressed.

Received 1/ 3/84. Revised 6/ 7/84. Revised 1/24/85. Accepted 2/ 4/85.