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Triggering of DNA strand breaks by 45/sup 0/C hyperthermia and its influence on the repair of. gamma. -radiation damage in human white blood cells

Journal Article · · Cancer Res.; (United States)
OSTI ID:5964403
Human peripheral white blood cells, freshly isolated from normal individual donors, were exposed to hyperthermia. Heat-generated 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/sup 0/ and 46/sup 0/C, for times up to 90 min. The time course of strand break induction at 45/sup 0/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/sup 0/C (10 to 20 min) initiated a cellular event which led to a rapid increase in the number of stand breaks during subsequent incubation of 37/sup 0/C. Continuous incubation at 45/sup 0/C produced less DNA damage than an initial period at 45/sup 0/C followed by incubation at 37/sup 0/C. This apparent triggering phenomenon was not due to a triggering of the respiratory burst in phagocytic cells, since no O/sub 2//sup -/ could be detected; in fact, a 30-min treatment at 45/sup 0/C largely blocked the capacity of the cells to respond normally to a soluble stimulator of the respiratory burst. Unlike ..gamma..-ray-induced breaks, 45/sup 0/C hyperthermia-induced breaks did not rejoin during subsequent incubation for up to 1 h at 37/sup 0/C. Additionally, 45/sup 0/C hyperthermia treatment progressively inhibited the ability of the cells to repair subsequent ..gamma..-ray-induced breaks (4 Gy). 17 references, 1 table.
Research Organization:
Atomic Energy of Canada Ltd., Chalk River, Ontario
OSTI ID:
5964403
Journal Information:
Cancer Res.; (United States), Journal Name: Cancer Res.; (United States) Vol. 42; ISSN CNREA
Country of Publication:
United States
Language:
English