MEASUREMENT OF INTRACELLULAR DNA DOUBLE-STRAND BREAK INDUCTION AND REJOINING ALONG THE TRACK OF CARBON AND NEON PARTICLE BEAMS IN WATER

Purpose: The study was aimed at the measurement of effect-depth distri butions of intracellularly induced DNA damage in water as tissue equiv alent after heavy ion irradiation with therapy particle beams. Methods and Materials: An assay involving embedding of Chinese hamster ovary (CHO-K1) cells in large agarose plugs and electrophoretic elution of r adiation induced DNA fragments by constant field gel electrophoresis w as developed. Double-strand break production was quantified by densito metric analysis of DNA-fluorescence after staining with ethidium-bromi de and determination of the fraction of DNA eluted out of the agarose plugs, Intracellular double-strand break induction and the effect of a 3 h rejoining incubation were investigated following irradiation with 250 kV x-rays and 190 MeV/u carbon- and 295 MeV/u neon-ions. Results and Conclusion: While the DNA damage induced by x-irradiation decrease d continuously with penetration depth, a steady increase in the yield of double-strand breaks was observed for particle radiation, reaching distinct maxima at the position of the physical Bragg peaks, Beyond th is, the extent of radiation damage dropped drastically. From compariso n of DNA damage and calculated dose profiles, relative biological effi ciencies (RBEs) for both double-strand break induction and unrejoined strand breaks after 3 h were determined, While RBE for the induction o f DNA double-strand breaks decreased continuously with penetration dep th, RBE maxima greater than unity were found with carbon- and neon-ion s for double-strand break rejoining near the maximum range of the part icles, The method presented here allows for a fast and accurate determ ination of depth profiles of relevant radiobiological effects for mixe d particle fields in tissue equivalent.