Hyperthermic Potentiation of the Effects of a Clinically Significant X-Ray Dose on Cell Survival, DNA Damage, and DNA Repair

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Abstract
Mouse leukemia L1210 cells grown in suspension were used to study the synergistic effects of combined hyperthermia (43, 45.5.degree. C) followed immediately by clinically significant X-ray doses (3-6 Gy [gray]). Cell survival was determined by growth in soft agar; the extent and repair of DNA single-strand breaks were measured by the alkaline elution technique. The degree of synergism for cytotoxic effects of heat and radiation (3 Gy) increased as a function of treatment time at 43 or 45.5.degree. C. Hyperthermia showed a greater synergistic effect with X-rays (3-6 Gy) at 43.degree. C than at 45.5.degree. C when compared at equal heat reductions in survival. The initial rate of repair of DNA single-strand breaks was inhibited; the extent of repair failed to reach 100% by 4 h with combined hyperthermia and the 3 Gy X-ray dose. These combined treatments showed synergism in terms of reducing cell survival. The reason for the incomplete repair of X-ray-induced DNA strand breaks with prior hyperthermic treatment was that the hyperthermia itself resulted in DNA strand breakage.